CN116635087A

CN116635087A - Vaccine composition

Info

Publication number: CN116635087A
Application number: CN202180081025.7A
Authority: CN
Inventors: U·A·贡佩尔斯
Original assignee: Vero Therapy Co ltd
Current assignee: Vero Therapy Co ltd
Priority date: 2020-10-08
Filing date: 2021-09-24
Publication date: 2023-08-22
Also published as: GB202107170D0

Abstract

A sterile pharmaceutical composition comprising one or more nucleic acid molecules comprising a plurality of immunogenic coding regions that collectively encode a plurality of herpes virus polypeptides, wherein the one or more nucleic acid molecules are capable of expressing the plurality of herpes virus polypeptides in an expression vector when introduced into a vertebrate cell, wherein each of the plurality of immunogenic coding regions has at least 90% sequence identity to the native coding region of a corresponding native full-length herpes virus polypeptide from the same herpesvirus species, wherein the plurality of herpes virus polypeptides are: (1) gD of herpes simplex virus 2 or herpes simplex virus 1; gE or gI of varicella zoster virus; gp350 or gp42 of epstein barr virus; gp42 of epstein barr virus selected from the group consisting of the gO of genotypes 1-8 of human cytomegalovirus; gO of human herpesvirus 6A; gO of human herpesvirus 6B; gO of human herpesvirus 7; or Kaposi's sarcoma-associated herpesvirus K8.1 (A/B); and (2) gB, gH and gL of the respective homologous human herpesviruses; and wherein the pharmaceutical composition is provided in a sealed sterile container for delivery.

Description

Vaccine composition

Technical Field

The present invention relates to vaccine or immune advanced therapy compositions, in particular polynucleotide vaccines, which are suitable for use against infectious agents, in particular herpes viruses.

Background

Human herpes viruses are a group of membrane-enveloped double-stranded DNA viruses responsible for significant global human morbidity and mortality (Knipe and Howley, 2013). All of these viruses use membrane fusion to initiate cell infection (Eisenberg et al 2012; vollmer and Grunewald, 2020). There are nine known human herpesvirus species, classified as (Davison et al 2009) (ictvaline. Org) HHV1, HHV2, HHV3, HHV4, HHV5, HHV6A, HHV6B, HHV7 and HHV8. These also include the ICTV classification and the generic name (i) HHV1, human alpha herpes virus type 1, with the generic list pure herpes virus type 1 (HSV 1); (ii) HHV2, human alpha herpes virus type 2, herpes simplex virus type 2 (HSV 2); (iii) HHV3, human alpha herpes virus type 3, varicella Zoster Virus (VZV); (iv) HHV4, human gamma herpes virus type 4, epstein Barr Virus (EBV); (v) HHV5, human beta herpes virus type 5, human Cytomegalovirus (HCMV); (vi) HHV6A, human beta herpesvirus type 6A; (vii) HHV-6B, human beta herpesvirus type 6B, and (viii) HHV7, human beta herpesvirus type 7; and (viii) HHV8 is Kaposi's sarcoma-associated herpesvirus (KSHV). In humans, these viruses cause a wide variety of diseases, the most severe of which are as follows. HSV1 causes oral and encephalitis, HSV2 causes genital and neonatal herpes, mortality and life-long disability, and VZV causes varicella and shingles. EBV causes infectious mononucleosis and is closely associated with several B cell lymphomas, nasopharyngeal carcinoma and gastric adenocarcinoma. HCMV causes severe infections in immunosuppressed patients and is one of the most common congenital infections, leading to hearing loss and a major non-genetic cause of life-long disability. HHV6A, HHV B and 7 cause infantile rosea (sixth disease), post-transplant limbic encephalitis, and are associated with neurological diseases, and HHV-8 can cause kaposi's sarcoma in several clinical settings, including in patients infected with Human Immunodeficiency Virus (HIV).

A common representative model of human herpesviruses and the model species of the "alpha" herpesvirus (subfamily alphaherpesvirus) subfamily are HSV. Despite intensive research, there is no effective vaccine against HSV1 or HSV2 and none is available against any other herpes virus other than VZV. However, much knowledge is available about HSV immune responses. More than 20 years of research have fully established that the envelope glycoprotein D of herpes simplex virus is a major immunogen. It causes binding of viruses to cells by attachment to cellular receptors, including within the TNF-R and Ig families, herpes virus invasion mediators (herpes virus entry mediator, HVEM), ligins or 3-O-sulfated-heparan sulfate (3-OS-HS) (Hilterbrand and Heldwein, 2019). The role of gD as a major immunogen was clearly demonstrated using subunit proteins prepared using recombinant antigens and using DNA encoding glycoproteins. Immunization with gD subunit proteins or encoding DNA provides some protection from acute aggressive infection in preclinical trials using murine and guinea pig infection models. Both produced neutralizing antibodies. Furthermore, clinical trials using HSV2 gD subunits in vaccine formulations with the chemical adjuvants alum and MPL showed effective production of neutralizing antibodies while protecting females from HSV1, but not HSV2 (Belshe et al 2012). The immune correlation of the protection of this assay was shown as the level of neutralizing antibodies (Belshe et al, 2014). Further boosting appears to be required to prepare a sufficiently protective HSV2 vaccine and it is postulated that other immune evasion glycoproteins may affect the response. Analysis of guinea pig infection models shows that this vaccine needs to be enhanced for protection (Bernstein, 2020; stanberry et al, 2002). However, it remains a useful comparison for evaluating new patterns of vaccination or immunotherapy against HSV1 and HSV2 infections.

Glycoprotein gD has been combined with other herpesvirus proteins in various proposed subunit protein vaccine formulations; and other formulations using genetically engineered viruses with gene deletions lacking gD have also been proposed. US 9,555,099 B2 discloses a vaccine composition comprising a recombinant HSV2 protein and an adjuvant; protein components, including envelope glycoproteins (such as gD) and structural proteins other than envelope glycoproteins (e.g., capsid or envelope proteins). US 7,094,767 B2 discloses DNA vaccines for HSV2 expressing full length HSV2 gD and/or truncated gB (another herpes virus envelope protein). US2019/0367561A1 relates mainly to vaccine compositions against EBV or HCMV and discloses antigen compositions comprising at least two Human Herpesvirus (HHV) polypeptides such as gp350 extracellular domain, gH extracellular domain, gL and gB extracellular domain, or encoding nucleic acids, involved in mediating HHV binding, fusion and entry into host cells. These may be combined with other polypeptides, such as gD, which means the possibility to combine the nucleic acid molecule and the polypeptide in the same composition. Methods for combining nucleic acid molecules and polypeptides in prime boost vaccination methods are known in the art (muthumanni et al, 2013). Typical studies have focused on truncated forms of polypeptides in order to avoid ER retention, e.g. in the case of gB, or secreted forms with gD to increase exogenous antigen exposure. While there are many possible combinations of herpesvirus polypeptides that may be included in a vaccine, many use primarily molecules that are exposed outside the virion or expand available epitopes without further reason, there is little evidence that combinations of polypeptides are more effective against viral challenge in vivo than gD immunization alone. In the guinea pig model, truncated gD is included; truncating gD plus gB and gH/gL; or a combination of gB and gH/gL, but no vaccine is significantly more effective than a vaccine comprising truncated gD as the sole polypeptide, and there is still a need for T cell boosting (Bernstein et al 2011).

The production and storage of polynucleotide vaccines may be simpler, safer and more economical than polypeptide vaccines, may stimulate cellular immunity, as antigens are produced intracellularly, and may be preferred for these reasons. However, they generally require adjuvant boosting (Liu, 2019). The vaccine effect may be modulated by different adjuvants or vectors for delivery of the polynucleotide. Polynucleotide vaccine studies have been more focused to date on increasing antigen dose via increased nucleic acid delivery or through the use of chemical or genetic adjuvants (Gary and Weiner,2020; grunwald and Ulbert,2015; liu, 2019).

There remains a need for effective herpesvirus vaccines, particularly rationally designed vaccines, which are designed based on well-defined scientific principles.

The listing or discussion of a prior-published document in this specification should not be taken as an acknowledgement that the document is part of the state of the art or is common general knowledge.

Summary of The Invention

In a first aspect the invention provides a pharmaceutical composition comprising one or more nucleic acid molecules comprising a plurality of immunogenic coding regions that together encode a plurality of herpes virus polypeptides, wherein the one or more nucleic acid molecules are capable of expressing the plurality of herpes virus polypeptides when introduced into a vertebrate cell, wherein each of the plurality of immunogenic coding regions has at least 90% sequence identity to the natural coding region of a corresponding native full length herpes virus polypeptide from the same herpes virus species, wherein the plurality of herpes virus polypeptides are:

(i) gD of herpes simplex virus 2 or herpes simplex virus 1; gE or gI of varicella zoster virus; gp350 or gp42 of epstein barr virus; gO selected from genotypes 1-8 of human cytomegalovirus; gO of human herpesvirus 6A; gO of human herpesvirus 6B; gO of human herpesvirus 7; or Kaposi's sarcoma-associated herpesvirus K8.1 (A/B); and

(ii) gB, gH and gL, respectively, associated with human herpesviruses; and is also provided with

Wherein the pharmaceutical composition is sterile and provided in a sealed sterile container.

In a second aspect the invention provides a pharmaceutical composition comprising a plurality of herpesvirus polypeptides associated with a lipid membrane, wherein the pharmaceutical composition is formed by expressing in human cells in vitro the plurality of herpesvirus polypeptides encoded by a nucleic acid comprising a plurality of immunogenic coding regions that collectively encode the plurality of herpesvirus polypeptides, wherein each of the plurality of immunogenic coding regions has at least 90% sequence identity to the native coding region of a corresponding native full length herpesvirus polypeptide from the same herpesvirus species, wherein the plurality of herpesvirus polypeptides are:

(ii) gB, gH and gL of the respective associated human herpesviruses.

Further aspects provide for use in medicine and methods of preparing the pharmaceutical compositions.

Brief Description of Drawings

Fig. 1: sequence alignment of the culture mutations in domain I showing glycoprotein gB structure in HSV2 and other herpesviruses.

Fig. 2: preventive HSV2 DNA vaccine trials against acute infection in preclinical models are described in example 3. The "VTL-VLMgD DNA" contains the HSV2 gene in the expression vector, i.e.encodes gD together with mutated gB, gH and gL.2A: protection from pathology showed complete protection by VTL-VLMgD DNA. 2B: protection from infection, showing inhibition of viral secretion following viral challenge. In VTL-VLMgD DNA immunized animals, no virus secretion could be detected by day 8 after virus challenge (0/12 animals any virus; p < 0.02).

Fig. 3: sequence alignment showing Rid1 HVEM interaction mutations in glycoprotein gD in HSV2 and other herpesviruses. The initial methionine is here +1 and the mature form is 26K+1.

Fig. 4: sequence alignment showing VZV fusion inhibiting mutations in glycoprotein gB in HSV2 and other herpesviruses. Fusion inhibition mutations in glycoprotein B VZV structures in the modeled conserved domains IV beta 23 and beta 30 sheets were aligned in reference strains of (a.) HSV1, HSV2, and VZV of the beta 23 sheet and (b.) HSV1, HSV2, VZV, EBV, CMV, HHV6A, HHV6B, HHV and HHV8 of the beta 30 sheet; all indicated amino acids were substituted with Ala.

Fig. 5: shows a pre-fusion stable mutation of HSV1 in glycoprotein gB domain III as displayed in HSV1 and is aligned herein with the human alphaherpesvirus HSV2 and VZV reference strains shown herein. Mutations of histidine to proline at position 516 in HSV1, 513 in HSV2, and 526 in the VZV gB amino acid sequence are indicated, with Pro substitution indicated by asterisks.

Fig. 6: preventive HSV2 DNA vaccine trials against acute infection in preclinical models are described in example 4. "gD DNA+VLM" contains the HSV2 gene in the expression vector, i.e., encodes gD together with mutated gB, gH and gL.6A: severity of acute lesions 4 to 14 days after virus challenge. Ratio = number of animals with lesions/cohort, showing lesion severity score data points and cohort median for individual animals. Full protection of all test animals (12 per cohort) by both VLM formulations is demonstrated. The positive control subunit vaccine showed only 75% protection, and the negative control had little protection with only 1/11 animals showing no lesions. 6B: severity of acute viral load. As indicated, in each of the queues 11-12, the mean and error bars (SEM) of the number of detectable viral loads of the animals are shown. Both VLM formulations provided two log reductions in viral titer 2 days after viral challenge and cleared the virus on day 8. Viruses were still detectable in the positive control subunit protein vaccine group, which overall showed less viral drop following challenge.

Fig. 7: prophylactic HSV2DNA vaccine trials against recurrent disease and virus reactivation in preclinical in vivo models are described in example 5. 7A: severity of recurrent lesions 15 to 63 days post virus challenge is shown by the number of days of cumulative recurrent lesions. Data points and median cohorts for individual animals are shown. Score = number of animals with lesions/cohort. VLM formulations combined with CCL5 showed a reduction in the number of recurrent variable days compared to VLM formulations alone or no vaccine treatment. 7B: protection from relapse as shown by the cumulative number of days of pathology for the mean of animals experiencing relapse in each cohort. In the gDNA+VLM/CCL 5 formulation, only half of the cohorts experienced any recurrence of lesions (6/12). Protection from relapse was observed only in VLM and CCL5 combinations and gD subunit protein vaccine positive controls compared to no vaccine treatment. 7C: resistance to recurrent viral shedding as measured by quantitative DNA PCR, qPCR (with SD). The data are the overall recurrence rate and cohort average for individual animals. Score = number of animals with detectable viral DNA/cohort. VLM formulations combined with CCL5 alone showed a significant reduction in viral shedding following viral reactivation. There was no reduction compared to the positive control gD subunit protein vaccine. 7D: protection against recurrent viral shedding occurs as measured by quantitative DNA PCR. Data are the average percentage of swab positive days. Score = total number of swab positive days per number of test for all animals in the cohort (days per number of animals in the cohort). A trend to protect against recurrent viral shedding was observed only in VLM in combination with CCL5 formulation. 180 available swabs were collected for each queue. In the no-vaccine group, a total of 165 swabs were collected.

Fig. 8: preventive HSV2 DNA vaccine trials against latent infection in preclinical models are described in example 5. 8A: protection against latent infection in Dorsal Root Ganglion (DRG), as measured by quantitative DNA PCR at day 63 post virus challenge. The data are mean values. Standard error bars (SEM) are indicated. All vaccine formulations provided a significant reduction in latent infection. 8B: as in 8A, but the data is presented as the number of individuals with detectable viral DNA (yes) and undetectable viral DNA (no). VLM formulations show a trend to protect against the establishment of latent infections in DRGs. 8C: protection against latent infection in the spinal cord as measured by quantitative DNA PCR at day 63 post virus challenge. The data are mean values. Error bars are SEM. All vaccine formulations provided a significant reduction in latent infection. 8D: as in 8D, but the data is presented as the number of individuals with detectable viral DNA (yes) and undetectable viral DNA (no). VLM formulations significantly reduce the number of animals with detectable viral DNA in the spinal cord.

Fig. 9: a prophylactic HSV2 DNA vaccine test against shedding of recurrent infectious virus in a preclinical model, as described in example 7, assessed the combined immunization of VLM and VIT. 9A: resistance to shedding of recurrent viruses, as measured by quantitative DNA PCR, qPCR, has SD. The data are the overall recurrence rate and cohort average for individual animals. Score = number of animals with detectable viral DNA/cohort. VLM formulations in combination with CCL5 showed a significant reduction in viral shedding following virus reactivation, whereas VLM formulations in combination with VIT showed a trend. There was no reduction compared to the positive control gD subunit protein vaccine. 9B: protection against recurrent viral shedding occurs as measured by quantitative DNA PCR. Data are the average percentage of swab positive days. Score = total number of swab positive days per number of test for all animals in the cohort (days per number of animals in the cohort). The trend to protect against recurrent viral shedding was observed only in VLM in combination with cytokine gene CCL5 or VIT. 180 available swabs were collected for each queue. In the no-vaccine group, a total of 165 swabs were collected. 9C: days to resist cumulative recurrent virus shedding were compared. In contrast to subunit protein gD vaccines that actually increased shedding days relative to no vaccine treatment, formulations containing VLM and cytokine genes CCL5 or VIT alone significantly reduced cumulative shedding days one and two months after virus challenge, p <0.05 indicated with asterisks.

Fig. 10: prophylactic HSV2DNA vaccine trials against recurrent infections causing disease lesions in preclinical models as described in example 7, the combined immunization of VLM and VIT was evaluated herein. 10A: severity of recurrent lesions 15 to 63 days post virus challenge is shown by cumulative number of days of recurrent lesions. Data points and median cohorts for individual animals are shown. Score = number of animals with lesions/cohort. VLM formulations and especially VIT in combination with CCL5 showed a reduced number of recurrent days compared to VLM formulation alone or no vaccine treatment. VLM and VIT formulations are the most effective and comparable to subunit proteins. 10B: protection from relapse as shown by the cumulative number of days of pathology for the mean of animals experiencing relapse in each cohort. In the gD DNA+VLM/CCL5 formulation, only half of the cohort experienced any recurrence of lesions (6/12), while more than half of the cohort in the gD DNA+VLM/VIT combination (7/12, 58%) was fully protected, and 100% of animals were protected from any vesicular disease. The greatest protection against recurrent disease was observed in VLM and cytokine gene combinations, VIT and gD subunit protein vaccine positive controls compared to no vaccine treatment.

Fig. 11: preventive HSV2 DNA vaccine trials against latent infection in preclinical models as described in example 7, and the combined formulation of vlm+vit DNA immunization was evaluated here. Protection against latent infection in Dorsal Root Ganglion (DRG), as measured by quantitative DNA PCR at day 63 post virus challenge. The data are mean values. Standard error bars (SEM) are indicated. All vaccine formulations provided a significant reduction in latent infection.

FIG. 12 neutralizing antibody titres of herpes simplex virus type 2 (HSV-2) in guinea pig serum after 2 intramuscular immunizations with vaccine formulations containing DNA encoding gD with VLM and DNA encoding cytokine CCL5 chemokine or VIT1 factor immunotherapeutic, compared to gD subunit protein vaccine formulations with mpl and alum or no vaccine treatment. * P <0.001 compared to no vaccine treatment is indicated.

Detailed description of the preferred embodiments of the invention

The present invention was developed using a novel strategy for presenting herpes virus polypeptides to the immune system in the form of a "virus-like membrane", wherein the herpes virus polypeptides responsible for cell binding and fusion are present in a natural interactive configuration associated with a lipid membrane as expressed in vivo. The presence of this form of herpes virus cell binding and fusion mechanism is believed to induce the natural complex of proteins and their transitional state, thereby mediating a cell fusion event in the immunized host. This may involve binding of the receptor to the host cell, triggering cell fusion by a conformational change in the polyprotein complex, then drawing the cell membranes together (mimicking the process by which the virus and cell membranes are drawn together during infection), and inducing cell fusion between adjacent membranes. These cell fusion events are believed to mimic infection of cells by the virus and elicit an innate immune mechanism that detects cell fusion as an impairment signal, thereby enhancing the ability to adapt immunity. Typically, the vaccine composition is provided as a polynucleotide vaccine, and the herpes virus cell binding and fusion mechanism is expressed and assembled in the host cell to produce a "virus-like membrane" in vivo. Polynucleotide vaccines can incorporate nucleotide compositions biased toward increasing CpG bias to induce innate mechanisms such as cellular immunity through the TLR9 signaling cascade. Alternatively, the "virus-like membrane" may be formed in vitro and provided in a vaccine composition, such as using a cell formulation or as an exosome.

In contrast to the typical approaches of polynucleotide vaccines that attempt to improve immune responses by increasing antigen doses or by means of synthetic adjuvants, our inventive "virus-like membrane" vaccine addresses the natural quality of the response and its efficacy via the generation of "fusion mechanisms". In addition, this approach differs from subunit protein vaccine formulations in that the glycoprotein is not present in the membrane and is therefore not in the desired fusogenic configuration.

Herpes virus mediated cell fusion is the first step required for infection (Hilterbrand and Heldwein, 2019). The inventors speculate that immune antibodies that inhibit cell fusion require an interactive architecture for components in the transition state between pre-and post-fusion complexes that mediate this process. In herpes simplex virus, there are four essential glycoproteins that mediate cell fusion in an in vitro cell assay (Hilterbrand and Heldwein, 2019). These include the immunogen gD, as well as the gH/gL complexes conserved in the fusion promoter gB and fusion regulator herpesviruses (Gompels et al, 1991; gompels and Minson,1989; hilterbrand and Heldwein, 2019). Transfection of the four genes encoding these HSV1 or HSV2 glycoproteins is necessary and sufficient to cause cell fusion (Turner et al, 1998). Although gH and gL form stable heterodimers, interactions between other components are transient and trigger a conformational change between pre-and post-fusion conformations. The crystal structure of post-fusion gB constructs has been determined, as reviewed in (Hilterbrand and Heldwein, 2019), and pre-fusion constructs have been determined using pre-fusion stable mutations (Vollmer et al 2020), but transitional states are under evaluation. Although there is evidence for interactions between gD, gB and gH/gL, these interactions appear to be transient. In summary, fusion complexes include the necessary and sufficient protein to effect fusion, and may include pre-or post-fusion forms, as well as variants that stabilize either form. Thus, the inventors speculate that, for an effective immune response, the immune host should be exposed to these transient pre-fusion and transitional state forms in order to block cell fusion and trigger the function of infection, as well as to increase effective immunity to naturally occurring structural epitopes as well as exposed linear sites.

Polynucleotide

In a first aspect the invention provides a pharmaceutical composition comprising one or more nucleic acid molecules comprising a plurality of immunogenic coding regions that together encode a plurality of herpes virus polypeptides, wherein the one or more nucleic acid molecules are capable of expressing the plurality of herpes virus polypeptides when introduced into a vertebrate cell, wherein each of the plurality of immunogenic coding regions has at least 90% sequence identity to the native coding region of a corresponding native full length herpes virus polypeptide from the same herpes virus species, wherein the plurality of herpes virus polypeptides are:

The one or more nucleic acid molecules of the pharmaceutical composition of the first aspect comprise a plurality of immunogenic coding regions that collectively encode a plurality of herpes virus polypeptides. Each immunogen encoding a different herpesvirus polypeptide. Multiple (e.g., all) immunogen encoding regions may be encoded by one nucleic acid molecule. Alternatively, at least one, such as each, immunogen encoding region may be encoded by a separate nucleic acid molecule. Any possible combination of nucleic acid molecules comprising multiple or single coding regions is contemplated, provided that one or more nucleic acid molecules collectively comprise multiple immunogen coding regions. The terms "nucleic acid molecule" and "polynucleotide" are used interchangeably herein and refer to a polymeric form of nucleotides of any length (deoxyribonucleotides or ribonucleotides), or analogs thereof. The one or more nucleic acid molecules may be deoxyribonucleic acid (DNA) polynucleotides, such as expressed by a suitable formulation, such as a synthetic expression DNA construct, a plasmid expression vector (such as a bacterial plasmid expression vector), or a viral expression vector (such as an adenovirus vector); or ribonucleic acid (RNA) polynucleotides, such as synthetic RNA, or expressed from an enzymatically modified plasmid expression vector to produce mRNA transcripts, which may include modified nucleosides as described herein. This can be prepared using a DNA plasmid to encode an RNA transcript that is transcribed by an RNA polymerase, followed by enzymatic 5 'capping and 3' polyadenylation reactions, followed by removal of double stranded RNA, followed by formulation in a lipid carrier nanoparticle as reviewed (Kowalzik et al 2021; rosa et al 2021) and as disclosed in WO2019/035066A1, for example. The formulation may also include auxiliary lipids, such as mRNA vaccines for known effective SARS-CoV2, such as 1, 2-distearoyl-sn-propanetriyl-3-phosphorylcholine (DSPC), cholesterol and/or diffusible PEG-lipids (2- [ (polyethylene glycol) -2000] -N, N-bitetradecylacetamide, PEG2000-DMA, such as for the SARS-CoV2 human vaccine BNT162b2, or 1, 2-dimyristoyl-rac-glycerol 3-methoxypolyethylene glycol-2000 and/or PEG2000-DMG, such as for the SARS-CoV2 human vaccine mRNA-1273), as reviewed in (Verbeke et al 2021). Alternative RNA species include viral vectors such as self-amplifying RNA (Blakney AK, ip S, gel AJ. An update on self-amplifying mRNA vaccine development. Vaccines (Basel.) 2021, month 1, 28; 9 (2): 97.doi:10.3390/vaccines 9020097). The one or more nucleic acid molecules are typically of the same type, such as all DNA or all RNA, but may comprise a combination of DNA and RNA. Both DNA and RNA formulations can be administered, for example, by intramuscular inoculation or other routes described herein, to generate protective immunity. The polynucleotide vaccine was shown to be effective in the first SARS-CoV2 mRNA vaccine approved for human use by two doses of vaccination at 28 day intervals intramuscularly (nucleoside modified RNA encoding spike glycoprotein, then encapsulated by lipid nanoparticles), as reviewed in (Lambe 2021).

As used in relation to the first aspect of the invention "pharmaceutical composition" is synonymous with "polynucleotide vaccine". Both terms mean that one or more nucleic acid molecules are isolated. The term "isolated" when used in the context of a nucleic acid molecule refers to a nucleic acid molecule that is substantially free of structures or compounds with which it is associated in its natural environment, and thus is distinguished from nucleic acid molecules that may naturally occur. For example, an isolated nucleic acid molecule is substantially free of cellular material or other polypeptides or nucleic acid molecules, including herpesvirus genomic material, from which a virus or source of infected cells may be derived. Thus, the pharmaceutical composition comprises one or more nucleic acid molecules encoding a particular herpes virus polypeptide (virus entering the cell fusion complex), but does not include other nucleic acid molecules that are also required to cause a viral infection.

A nucleic acid sequence that "encodes" a selected polypeptide is a nucleic acid molecule that is transcribed (in the case of DNA) and translated (in the case of mRNA) into the polypeptide in vivo when under the control of appropriate regulatory sequences. By "immunogen coding region" is meant the Open Reading Frame (ORF) encoding the immunogen, typically also comprising a 5' kozak sequence operably linked to the ORF. The boundaries of the open reading frame are determined by a start codon at the 5 '(amino) terminus and a translation stop codon at the 3' (carboxyl) terminus. By "immunogen" is meant a coded herpes virus polypeptide that is expressed in vivo after administration of the pharmaceutical composition. One or more nucleic acid molecules are capable of expressing a plurality of herpes virus polypeptides when introduced into a vertebrate cell. This can be achieved by virtue of the following characteristics. In the case of DNA molecules, the immunogen encoding region is operably linked to a 5' promoter capable of driving transcription of the immunogen encoding region in vertebrate cells, such as via promotion of RNA polymerase II binding. The immunogen encoding region is typically adjacent to a 3 'untranslated region comprising a 3' polyadenylation sequence and terminates with a transcription termination sequence. In the case of RNA molecules, the immunogen encoding region is typically adjacent to a 3 'untranslated region comprising a 3' polyadenylation sequence and terminates with a transcription termination sequence. The ability to be expressed in vertebrate cells typically involves expression in cells of the vertebrate species (typically mammal, typically human) for which the pharmaceutical composition is intended. The expression of the herpes virus polypeptide in the cell can be detected in vitro by means known to the skilled person. Suitable methods for detecting polypeptides expressed in cells may use assays formed by multinucleated cells or use immunofluorescence or western blotting (Muggeridge, 2000; rogalin and Heldwein,2016; turner et al, 1998).

According to a first aspect, each of the plurality of immunogen encoding regions has at least 90% sequence identity to the native encoding region of a corresponding native full length herpesvirus polypeptide from the same herpesvirus species. The relatedness between two nucleotide sequences (or between two amino acid sequences) is described by the "sequence identity" parameter.

Suitably, each of the plurality of immunogen encoding regions has at least 95% sequence identity, such as at least 97% sequence identity, at least 99% sequence identity, at least 99.5% sequence identity or 100% sequence identity, to the native encoding region of the corresponding native full-length herpesvirus polypeptide. This level of sequence identity can be observed over the full length of the relevant SEQ ID NO sequence. Thus, an immunogen coding region typically exhibits at least 95% sequence identity to the native coding region of the corresponding native full-length herpesvirus polypeptide, either by itself being full length or by having at least 95% aligned length to the native coding region of the full-length herpesvirus polypeptide. Typically, the length of the alignment is at least 96%, 97%, 98%, 99%, 99.5% or 100%. Typically, the length of the alignment is 100% and the sequence identity is at least 96%, 97%, 98%, 99%, 99.5% or 100%.

Suitably, each of the plurality of immunogen encoding a herpes virus polypeptide having at least 90% sequence identity to a corresponding native full length herpes virus polypeptide encoded by a native encoding region from the same herpes virus species. Suitably, the level of sequence identity between a herpes virus polypeptide and the corresponding native full length herpes virus polypeptide is at least 96%, 97%, 98%, 99%, 99.5% or 100%. This level of sequence identity can be observed over the full length of the relevant SEQ ID NO sequence. Thus, a herpes virus polypeptide typically exhibits at least 90% sequence identity to the corresponding native full-length herpes virus polypeptide, either by itself being full-length or having an aligned length of at least 90% to the native full-length herpes virus polypeptide. Typically, the length of the alignment is at least 96%, 97%, 98%, 99%, 99.5% or 100%. Typically, the length of the alignment is 100% and the sequence identity is at least 96%, 97%, 98%, 99%, 99.5% or 100%.

The presence of a transmembrane domain in a herpes virus polypeptide having a transmembrane domain in its native form is believed to be important. The presence of a transmembrane domain, such as in a variant of a herpes virus polypeptide, can be predicted by methods known in the art, for example reviewed in Nugent and Jones, 2009. In the case of HSV1 and HSV2, gB, gH and gD each comprise a transmembrane domain. For association with the membrane or secretion, gB, gH, gD and gL all comprise N-terminal signal sequences that they are capable of inserting into the coarse endoplasmic reticulum RER and co-translating into the RER lumen and subsequently cleaving the signal sequences by signal recognition granule proteolytic processing. The ability of the N-terminal sequence of a herpes virus polypeptide (e.g., variant) to act as a signal sequence can be predicted by methods known in the art (Nugent and Jones, 2009). Thus, each of gB, gH, gD, and gL encoded by an immunogen encoding region should comprise a functional N-terminal signal sequence. gB. The gH and gD encoded molecules have a second transmembrane domain that allows for intracembrane homocytoplasmic exposure, and a positively charged termination anchor sequence that allows for intercalation into the membrane. While the expressed gL is a secreted protein in nature and lacks a transmembrane domain, it associates with the membrane via its formation of a heterodimer with gH. All native HSV1 and HSV2 gB, gH, gD and gL glycoproteins undergo post-translational glycosylation during the intercalating membrane and are processed via the pathway through exocytosis, and glycosylation may be important for architecture and function. It is preferred that the herpes virus polypeptide encoded by the immunogen encoding region comprises a native glycosylation site. Glycosylation is N-linked or O-linked and the consensus sequence is predominantly NXT/S or at a site on T, S, respectively, as reviewed in Hamby and Hirst, 2008. Native HCMV gB contains palmitoylation sites, which can increase cell fusion in C777 (strain VR 1814) (Patrone et al 2016) and Merlin reference strain C779. Preferably, the polypeptide encoded by the immunogen encoding region (e.g. gB) comprises a palmitoylation site when present in the native polypeptide.

gD glycoproteins bind to TNF receptor superfamily LIGHT and act as checkpoint inhibitors, giving natural boost of immune responses via blocking of the down-regulation system (Cai and Freeman, 2009). Thus, if this receptor-ligand relationship is maintained, this may increase the type of immune response. The interaction domain has been localized to the outer part of the molecule, but correct folding of the membrane tethered form as expressed by the whole gene may facilitate interaction between the interacting immune cells and glycoprotein-expressing cells (Cairns et al, 2019; lu et al, 2014). Thus, it is preferred that gD maintains the ability to bind TNF receptor superfamily LIGHT, as described in Cai and Freeman,2009.

For the purposes of the present invention, the sequence identity between two amino acid sequences is determined using the Needleman-Wunsch algorithm (Needleman and Wunsch,1970, J.mol. Biol. 48:443-453) as implemented in the Needle program of the EMBOSS package (EMBOSS: the European Molecular Biology Open Software Suite, rice et al, 2000,Trends Genet.16:276-277), preferably in versions 5.0.0 or later. The parameters used are a gap opening penalty of 10, a gap expansion penalty of 0.5, and an EBLOSUM62 (the emoss version of BLOSUM 62) substitution matrix. The output of the "longest identity" of the Needle label (obtained using the-nobrief option) was used as percent identity and calculated as follows:

(identical residues×100)/(alignment length-total number of gaps in the alignment).

"variant" refers to a protein in which amino acid insertions, deletions, or substitutions (either conservative or non-conservative) are present at one or more positions. A "variant" may have modified amino acids. However, as noted above, it is preferred that the variant retains the same N-linked and O-linked glycosylation sites as the native protein, as well as palmitoylation sites (where present).

For the purposes of the present invention, sequence identity between two deoxyribonucleotide sequences is determined using the Needleman-Wunsch algorithm (Needleman and Wunsch,1970, supra) as implemented in the Needle program of the EMBOSS package (EMBOSS: the European Molecular Biology Open Software Suite, rice et al, 2000, supra), preferably in versions 5.0.0 or later. The parameters used are a gap opening penalty of 10, a gap expansion penalty of 0.5, and an EDNAFULL (an embos version of NCBI NUC 4.4) substitution matrix. The output of the "longest identity" of the Needle label (obtained using the-nobrief option) was used as percent identity and calculated as follows:

(identical deoxyribonucleotides. Times.100)/(length of alignment-total number of gaps in alignment).

The corresponding (or reference) natural coding region to which the immunogen coding region is compared is from the same herpesvirus species, typically from the same herpesvirus strain. In an alternative form, the corresponding (or reference) native full-length herpes virus polypeptide to which the herpes virus polypeptide is compared is encoded by a native coding region from the same herpes virus species (typically from the same herpes virus strain). The various herpesvirus polypeptides are:

(ii) gB, gH and gL of the respective associated human herpesviruses.

In any given herpesvirus species, the above four polypeptides form a fusogenic complex of the herpesvirus when assembled together in proper association with the lipid membrane. In other words, one or more nucleic acid molecules are capable of expressing a plurality of herpes virus polypeptides in the form of a herpes virus fusion complex when introduced into a vertebrate cell. By "fusogenic complex (fusogenic complex)" or "fusion complex" we mean that the polypeptide is necessary and sufficient for cell fusion when co-expressed in vertebrate cells. Fusion complexes are formed from core fusion mediators gB, gH, gL together with a cell-binding glycoprotein component as disclosed in (i) above. Therefore, gB, gH, gL and gD of HSV2 strain are required for the strain of HSV 2. For the strain of VZV, any one of gB, gH, gL and gE or gI of the VZV strain is required. By "gB, gH, gL of the respective associated human herpesviruses", we mean that the gB, gH and gL herpesvirus polypeptides mentioned in (ii) above may be derived from the same herpesvirus species, typically the same herpesvirus strain as the herpesvirus polypeptide selected from (i) above. Thus, where the first polypeptide may be derived from a gD of herpes simplex virus type 2, gB, gH and gL may also typically be derived from the same strain of herpes simplex virus type 2. Where the first polypeptide may be derived from a gD of herpes simplex virus type 1, gB, gH and gL may also typically be derived from the same strain of herpes simplex virus type 1. By "derivable" we mean that the immunogen encoding region has at least 90% sequence identity to the native encoding region of the corresponding native full length herpes virus polypeptide; or the polypeptide has at least 95% sequence identity to a corresponding native full-length herpesvirus polypeptide. Thus, each of the four herpesvirus polypeptides need not be identical to a herpesvirus polypeptide from the same strain. By "gO selected from human cytomegalovirus genotypes 1-8" we mean genotypes known in the art as gO1a, gO1b, gO1c, gO2a, gO2b, gO3, gO4, gO5a/gO5, such as those provided in Table 1.

Where a surrogate is present for one of the polypeptides of the fusion complex, one or more nucleic acid molecules may encode one or more than one such polypeptide. Thus, for a VZV strain, any or both of gB, gH, gL, and gE and gI of the VZV strain may be encoded and expressed by one or more nucleic acid molecules. In embodiments, the pharmaceutical composition comprising one or more nucleic acid molecules does not comprise a nucleic acid molecule encoding or capable of expressing a herpes virus polypeptide other than: (i) Those that form fusion complexes that are core fusion mediators gB, gH, gL and a cell-binding glycoprotein component as disclosed herein, accepting that in the presence of a cell-binding glycoprotein surrogate, one or more surrogate may be present; and optionally (ii) a viral immunomodulator, typically a secreted viral immunomodulator, such as a chemokine as disclosed herein. Thus, the herpesvirus polypeptides encoded by one or more nucleic acid molecules may be limited to those that form fusion complexes, and optionally also herpesvirus immunomodulators.

HSV2 or HSV1 gD, although not direct fusion proteins, trigger fusion mechanisms and serve as natural immune checkpoint inhibitors to boost the immune response by virtue of binding to its receptor (preventing BTLA from binding to CD 160-HVEM) (Lasaro et al 2005; zhang and Ertl, 2014) and also via interaction with a subset of dendritic cells (Porchia et al 2017). The gD molecule also binds to a second receptor connector and interaction with a corresponding ligand can affect the nature of the immune response. For example, reducing or eliminating interactions with HVEM may increase IgG2 ADCC antibody-dependent cytotoxicity (Burn Aschner et al 2020), while retaining such interactions may increase IgG1 neutralizing antibodies. SNP variant modifications may reduce interactions with HVEM as shown by strain ANG and Rid1 variant viruses (Montgomery et al, 1996), and this is introduced in HSV2 gD in SEQUENCE ID65 and reference HSV1 gD in SEQUENCE ID 63. Thus, the use of wild-type gD2 can stimulate neutralizing antibodies as shown, with utility for controlling e.g. HIV1 (Kadelka et al, 2018) and other IgG1 responses that avoid adcc—this is important where antibody-dependent enhancement of ADE responses may be detrimental due to increased infection as known for dengue and coronaviruses, and thus has utility for targeting these viruses (s.et al, 2020). Whereas mutant SNP gD2 with reduced interaction with HVEM has the effect of stimulating IgG2 ADCC response and controlling HSV infection. This approach is also effective for therapeutic vaccines, for example, where the individual has been seropositive for HSV, then a DNA vaccine is provided with a VLM containing a variant gD encoded to enhance ADCC, as shown for HSV2 with a gD deletion used as an immunogen (Burn Aschner et al 2020). This is based on variant SNPs in Rid1 HSV1 gD and deletion studies on HSV2 gD. Here, the SNP was transposed to the reference HSV1 strain 17 and HSV2 gD by alignment (FIG. 3, table 4; sequence IDs 63 and 65; and translated polypeptide sequences SEQ ID NO.64 and 66). Suitably, the gD polypeptide encoded by the immunogen encoding region of gD comprises a mutation that reduces interaction with HVEM receptors, such as a substitution at a position corresponding to position 52 of SEQ ID 64.

Similar to the SNPs in gD, SNP variants in HSV2 gB may also redirect immune responses, in this case early pre-fusion forms of glycoproteins, as indicated by SEQUENCE ID 71-74. This is based on a study of VZV gB and shows here that HSV2 gB (fig. 4, table 4) was analyzed using an alignment, followed by SNP mutation of the amino acid codons in all representative human herpesvirus-encoded gB molecules, such as SEQUENCE ID 67-70. The wild-type encoded amino acids are displayed in a conserved structural fold of gB in domains DIV beta 23 and beta 30 (Oliver et al 2020). The first set of pre-fusion like gB variants are conserved in the domain DIV beta 23-sheet alpha herpes virus, as shown in fig. 4A, and represented by SEQUENCE IDs 67, 68, 71, 72, 75 and 76. The second set of pre-fusion like gB variants are conserved in human alpha, beta and gamma herpes viruses, as shown in fig. 4B, domain divβ30 sheet in table 4, and are represented as encoded by SEQUENCE IDs 69, 79, 73, 74, 77, 78 and 79-90. These variants can form complexes of membrane associated glycoproteins, but do not perform cell fusion, and therefore will escape innate signaling through TLR7 and have utility in presenting epitopes to stimulate antibody production to inhibit the transition to cell fusion required for cell infection. They will retain the ability to express endogenously, thereby stimulating cellular immunity also via antigen presentation by MHC molecules on the cell surface.

Additional different pre-fusion stable mutations of the SNPs in gB are shown in fig. 5, table 4, as disclosed for HSV1 (Vollmer et al 2020), and are represented by SEQUENCE IDs 131, 132 and 133, including HSV2 and VZV gB SNPs identified by the alignment herein (fig. 5).

Suitably, the gB polypeptide encoded by the immunogenic coding region of gB comprises a mutation that stabilizes gB in trimers in the pre-fusion construct, such as a mutation in gB domain III and/or IV, such as a substitution at a position corresponding to one or more of the substitutions in SEQ ID 67 to 90 or 132 to 134.

Typically, the ability of a native polypeptide (or a polypeptide encoded by an immunogenic coding region) to mediate cell fusion is measured in vertebrate cells of the same species (typically mammalian species, typically human) for which the pharmaceutical composition is intended. Methods for detecting cell fusion due to co-expression of polypeptides of the fusogenic complex are described in Turner et al, 1998. Cell fusion can be detected by the formation of multinucleated cells (i.e., cells having more than one nucleus). For example, monolayers of Cos cells can be transfected with plasmids from which the fusion-promoting complex polypeptides are expressed, covered with VERO cells or other allowable cell types, and multinucleated cells detected by nuclear staining. Cell fusion is considered to occur when there are more multinucleated cells with the least number of nuclei (e.g., 10) after transfection with the plasmid from which the fusion promoting complex polypeptide is expressed than in mock transfected cells. Typically, the number of multinucleated cells after transfection with a plasmid from which the fusion-promoting complex polypeptide is expressed may be at least 2-fold, such as at least 5-fold, such as at least 10-fold as many. Similarly, using the same assay, these fusion effects can be compared to mutations or variants of these proteins that are capable of stabilizing the fusion form, e.g., a pre-fusion stabilizing mutation will prevent pro-fusion transition and reduce multinucleated cell formation.

Preferably, the reference herpesvirus strain compared to the herpesvirus polypeptide encoded by the immunogen encoding region is a representative clinical isolate of the epidemic strain seen in the infected population (typically the infected population). Isolated strains and related nucleic acid sequences can be subjected to deep next generation sequencing, thus allowing control of any effects of the strain population and identification of representative dominant wild-type sequences. Clinically prevalent strains of herpes virus, their genomic sequences and nucleic acid sequences encoding defined polypeptides are known in the art. Representative examples are included in table 1. Polypeptide sequences are also known per se and can be obtained by translation of the open reading frame of the nucleic acid sequence.

Table 1: reference HHV species and strains containing related nucleic acid sequences having accession numbersVariants with sequence ID

/>

The herpes virus polypeptides encoded by the immunogen encoding regions are suitably all derived from the same herpes virus strain, in the sense that they are substantially identical to the corresponding native full length herpes virus polypeptides encoded by the individual strains. Derivatization from a single strain may facilitate the formation of the native conformation of the polypeptide associated with the lipid membrane when expressed in a host cell. This may also contribute to the natural formation of natural fusogenic complexes, as there is evidence that glycoproteins from different strains bind different properties. However, the herpesvirus polypeptides encoded by the immunogen encoding regions may alternatively be derived from different herpesvirus strains within the same herpesvirus species. For example, as shown in table 1, there are nine variants of HCMV gO. The gO derived from one strain may be combined with gB, gH and gL from another strain. Because the coding sequences for gB, gH, and gL are similar among the different strains, each of the multiple immunogenic coding regions encoding a herpes virus polypeptide still has at least 95% sequence identity to the corresponding native full-length herpes virus polypeptide encoded by the native coding region from the same herpes virus strain. Likewise, there are several variants of KSHV gk 8.1. gK8.1 from one strain may be combined with gB, gH and gL from another KSHV strain. For the avoidance of doubt, where reference is made to the gO of HCMV, the gO may be any variant of gO which is present in a different HCMV strain. The gO of HHV6A should be construed accordingly to encompass any variant of gO present in different HHV6A strains; and the gO of HHV6B and K8.1 of KSHV should be interpreted accordingly.

The examples use wild-type sequences from natural strains of the human population HSV2, i.e.reference sequences. All genes have wild-type sequences from the same reference strain as displayed in the human population (Szpara et al, 2014). These have all been subjected to deep next generation sequencing, thus allowing control of any effect of the strain population and synthesis of a representative dominant wild-type sequence (reference to human alphaherpesvirus 2, hsv2, strain HG52, NCBI accession NC 001798). All versions of the sequence were checked in NCBI Genbank (versions 7-2019 to 7-2020) and the updated NGS depth sequencing reference to verify any mutations and correct the relevant sequences.

Codon usage, cpG bias and G+C content

In one embodiment, each of the plurality of immunogen encoding regions has substantially the same codon usage, cpG bias and/or g+c content as the codon usage, cpG bias and/or g+c content of the native encoding region of the corresponding native full-length herpesvirus polypeptide. Typically, the codon usage, cpG bias and g+c content of the native coding region of the corresponding native full-length herpesvirus polypeptide are the same for the entire herpesvirus genome. However, for CMV, HHV-6A/B and HHV-7, only one region of the genome was CpG inhibited, and this was outside of the fusion complex genes described herein. Human genes have CpG inhibition, which is not common in vertebrate coding sequences, due to the mutagenic effect of deamination to T residues following C methylation, cpG mutations are either TpG or complement CpA, whereas herpesviruses have different CpG inhibition relative to the site of incubation. Alpha herpesviruses HHV1, HHV2 and HHV3 were not CpG inhibited, beta herpesviruses HHV5, HHV6A and HHV6B were essentially not CpG inhibited except for immediate early genes, whereas gamma herpesviruses HHV4 and HHV8 were CpG inhibited (Honess et al, 1989). Furthermore, HHV1 and HHV2 have increased CpG prevalence given that the C+G composition of HHV1 and HHV2 exceeds that of human genes. The g+c content was different in the corresponding genome, with a median value of 67.5% HHV1, 70% HHV2, 46% HHV3, 55.4% HHV4, 57.3% HHV5, 42.4% HHV6A, 42.8% HHV6b, 36.2% HHV7, 53.8% HHV8 compared to the median value of 41% for the human gene.

Codon usagePrevious studies have focused on optimizing codon usage to increase antigen production. Recent data, however, shows that this can alter the folding of the polypeptide (Athey et al, 2017). Proper folding of the polypeptides of the fusogenic complex is required for the regulation of the pre-and post-fusion and transitional states and is an integral part of the function. Certain codons of a particular amino acid are expressed as specific biases by various species. Since each codon consists of three nucleotides, while the nucleotides making up the DNA are limited to four specific bases, there are 64 possible combinations of nucleotides, of which 61 encode amino acids (the remaining three codons encode signals that terminate translation). The "genetic code" showing which DNA codons encode which amino acids is reproduced herein as table 2. The corresponding genetic code applies to the RNA codon, except that uracil (U) is present in the RNA in place of thymine (T). Thus, many amino acids are specified by more than one codon. This degeneracy allows the base composition of a polynucleotide to vary over a wide range without altering the amino acid sequence of the protein encoded by the polynucleotide.

Table 2: standard genetic code

Many organisms exhibit a bias of using specific codons to encode specific amino acids inserted in a growing peptide chain. Codon preference or codon bias, i.e., the difference in codon selection between organisms, is provided by the degeneracy of the genetic code and is well documented in many organisms. Codon bias is generally related to the efficiency of translation of messenger RNA (mRNA), which in turn is believed to depend on, inter alia, the nature of the codons being translated and the availability of specific transfer RNA (tRNA) molecules. The selected tRNA's that are dominant in the cell typically reflect codons that are most frequently used in peptide synthesis.

Codon usage tables for a given organism can be readily obtained, e.g. "secret" at www.kazusa.or.jp/codon/gainA codon usage database (Codon Usage Database) ". A comprehensive analysis of codon usage for 43 herpes viruses sequenced throughout the genome is found in Fu, m.codon use bias in hepesvirus.arch Virol 155,391-396 (2010);https://doi.org/10.1007/s00705-010-0597-0. The codon usage table for HHV2 is reproduced below as table 3.

By using these or similar tables, one of ordinary skill in the art can apply frequencies to any given polypeptide sequence. The difference in codon usage between sequences can be expressed as a percentage difference in the frequency of a given codon for a given amino acid between the two sequences. For example, gly may be encoded by GGC at a frequency of 30% in one sequence, but 20% in a different sequence. The frequency difference was 10%. The frequency difference for each of the 64 codons of the two sequences can be determined and averaged as the average frequency difference. By "substantially identical" codon usage to the codon usage of the native coding region of the corresponding native full-length herpesvirus polypeptide we mean that the average frequency difference between the codons in the immunogen coding region and the native coding region is less than 5%, such as less than 2%, less than 1%, less than 0.5%, less than 0.1%. For example, the codon usage for HHV1 and HHV2 is compared in Table 3, and GGC encoded Gly is 34% in HHV2 and 29% in HHV 1. Preferably, the codon usage is identical to the native coding region of the herpes virus polypeptide.

Table 3: codon usage table comparing HHV2 (upper panel) with HHV1 (lower panel)

The different codon usage tables generated for each herpesvirus can be used for different herpesvirus genes. For example, HSV has a high g+c bias and no CpG inhibition, and thus can be sensed by TLR9 receptors to stimulate innate immunity. The codon usage table can be similarly applied to other herpesvirus genes without such a composition. Similarly, HHV-6A, B and HHV-7 have low g+c bias and certain regions of the genome are CpG inhibited, these codon usage tables can be used to create genes in other herpesviruses in order to avoid TLR9 receptor innate immune signaling while being able to evade detection of zinc finger antiviral protein ZAP, which binds to high CpG regions to target degradation.

CpG bias and g+c content.CpG sites or CG sites are regions of a polynucleotide in which a cytosine nucleotide follows a guanine nucleotide in its 5 '. Fwdarw.3' direction in a linear sequence of bases. The frequency of CG in a given polynucleotide sequence is a function of codon usage. By "CpG bias" we mean the frequency of CpG dinucleotides in a gene. The frequency in one coding sequence may be 3%, but in a different sequence it may be 1%. The frequency difference was 2%. Deviations in dinucleotide frequency are expected to be reported by CG composition and codon usage. In gamma herpes viruses, cpG inhibition was observed to be between 1.5-3.0% compared to expected (Honess et al, 1989). By "substantially identical" CpG bias to the CpG bias of the native coding region of the corresponding native full-length herpesvirus polypeptide, we mean that the difference in CpG frequency between the immunogenic coding region and the codons in the native coding region is less than 3%, such as less than 1%, such as less than 0.5%, such as less than 0.1%. "G+C content" is the frequency of bases G and C in a polynucleotide sequence and is also a function of codon usage. The frequency in one coding sequence may be 60%, but in a different sequence it may be 40%. The frequency difference was 20%. For example, the g+c median composition of HHV2 is 70%, while HHV7 is 36%. In contrast, the median g+c composition was 67.5% and 70% between two closely related alpha herpesviruses HHV1 and HHV2, respectively, or 42.4% and 42.8% for two closely related gamma herpesviruses HHV6A and HHV 6B. By "G+C content" substantially identical to the G+C content of the native coding region of the corresponding native full-length herpesvirus polypeptide, we mean the G+C content between the immunogen coding region and the codons in the native coding region The difference in frequency is less than 5%, such as less than 2%, such as less than 1%, such as less than 0.5%. It has long been observed that CpG dinucleotides occur in vertebrate genomic sequences at a much lower frequency than would be expected due to random chance, a phenomenon known as CpG suppression. HSV1 and HSV2 genomic sequences are constitutively biased towards high G+C levels and are not CpG-inhibited (Honess et al, 1989; szpara et al, 2014). Thus, genes from these viruses in natural codon usage can naturally stimulate the innate signaling mechanisms of TLR9 to naturally boost the immune response, rather than adding synthetic CpG oligonucleotides as adjuvants. In contrast, the use of sequences with CpG inhibition, such as in gamma herpes viruses, can evade recognition of ZAP proteins and subsequent targeted degradation (Takata et al, 2017).

Non-coding functional motifs and sequences

Kozak sequence.In one embodiment, each of the plurality of immunogen encoding regions comprises a Kozak sequence capable of allowing translation of the herpes virus polypeptide to be initiated in a vertebrate cell with an efficiency that is substantially the same as the efficiency with which the Kozak sequence of the native encoding region of the corresponding native full-length herpes virus polypeptide allows translation to be initiated in a vertebrate cell, such as wherein the Kozak sequence of each of the plurality of immunogen encoding regions is the same as the Kozak sequence of the native encoding region of the corresponding native full-length herpes virus polypeptide. Kozak sequences are nucleic acid motifs that are used as protein translation initiation sites in most eukaryotic mRNA transcripts. The sequence was initially defined as 5' - (gcc) gccRcc AUGG-3 (IUPAC nucleobase symbols are summarized herein), wherein underlined nucleotides indicate the translation initiation codon, encoding methionine; capital letters indicate highly conserved bases, i.e., the "AUGG" sequence is constant or rarely (if ever) changed; "R" indicates that a purine (adenine or guanine) is always observed at this position; lowercase letters represent the most common base at positions where the base may still vary; and the sequence (gcc) in brackets is not clearly understood. See Kozak M (1987) "An analysis of 5' -noncoding sequences from 699vertebrate messenger RNAs". NuThe nucleic Acids Res.15 (20) 8125-8148.Doi:10.1093/nar/15.20.8125. For example, the Kozak sequence of the gH coding region of HSV2 strain HG52 is ACGACCATGG (initiation codon underlined). Variations within the Kozak sequence change their "strength". Kozak sequence strength refers to the degree of advantage of initiation, thereby affecting how much protein is synthesized from a given mRNA (Kozak, 2005). The strength of the Kozak sequence (Kozak, 2005) can be measured in vertebrate cells by means known in the art, and typically in cells of the species (typically mammalian species, typically human) for which the pharmaceutical composition is intended (Hernandez et al 2019). Suitably, each of the immunogen encoding regions comprises a native Kozak sequence, so initiation of translation may occur sequentially as during natural infection of the cell.

3' untranslated region.In one embodiment, each of the immunogen encoding regions is operably linked to a3 'untranslated region (UTR) that allows for substantially the same degree of mRNA stability of the immunogen encoding region or transcript thereof, such as by comprising the same 3' polyadenylation sequence. The 3' UTR was found to immediately follow the translation termination codon and play a key role in translation termination and post-transcriptional modification. Polyadenylation is the addition of poly (A) tails to messenger RNA. The poly (a) tail consists of a plurality of adenosine monophosphates, such as 10 to 300 adenosine monophosphates. In eukaryotes, polyadenylation is part of the process of producing mature messenger RNAs (mrnas) for translation. The polyadenylation process begins with the termination of gene transcription. The 3' -most segment of the newly made pre-mRNA is first cut out by a set of proteins; these proteins then synthesize a poly (A) tail at the 3' end of the RNA. The poly (A) tail is important for nuclear export, translation and stability of mRNA. The tail shortens with time and when it is short enough, the mRNA is degraded by the enzyme. The 3' polyadenylation sequence comprises the highly conserved AAUAAA sequence 12-30nt upstream of the cleavage site and up to 30nt downstream of the U-or GU-rich sequence. Suitable 3' polyadenylation sequences are derived from SV40 virus, as provided in standard expression vectors, and in preferred embodiments are derived from pCDNA3.1. All gene insertions in the plasmid expression vector include only 3' termination codons The codons are then followed by the standard 3' untranslated region of a plasmid expression vector as set forth above. In the examples, all herpes virus polypeptide genes expressed as in plasmid expression vectors contain the same 3' polyadenylation sequence, in this case as in standard SV40 expression vectors, as described for pcDNA3 derived vectors (Invitrogen, thermosusher), including the pCMV6 series (origin) (Andersson et al, 1989). Although differences in 3' sequences in viral genes may affect RNA stability and turnover rate (glausinger and Ganem, 2006), here four genes are coordinately expressed and stable.

A promoter.In embodiments in which one or more nucleic acid molecules are deoxyribonucleic acid (DNA) polynucleotides, each of the immunogen encoding regions is operably linked to a 5' promoter. Suitably, each coding region operably linked to a 5 'promoter is capable of simultaneous gene expression in a vertebrate cell, such as by virtue of each coding region being linked to the same 5' promoter. A promoter is a sequence of DNA to which a protein binds, from which mRNA transcription is initiated from downstream DNA. Suitably, a high expression promoter sequence is used. Suitably, the expression is constitutive in vertebrate cells. In mammalian cells, useful promoters may be obtained from Cytomegalovirus (CMV) and CAG hybrid promoters (hybrids of CMV early enhancer element and chicken β -actin promoter) or simian cavitation virus 40 (SV 40). Particularly suitable high expression promoters are derived from the immediate early genes of human cytomegalovirus (as in US 5385839A) (Thomsen et al, 1984), as utilized in the preferred embodiments of the standard gene expression plasmid vector pCDNA3.1 or pCMV6 and related derivatives. In an embodiment, the plasmid is designed with a promoter as is standard in gene therapy applications, so that all gene products can be expressed simultaneously, unlike in virus-infected cells where the fusion modulator gH/gL is tightly controlled for expression as a "late" gene only after DNA replication, while gD and gB are expressed early after infection.

Control sequences.The nucleic acid molecule may, where appropriate, comprise one or more further control sequences. The term "control sequence" means the code bookAll nucleic acid sequences necessary for expression of the polynucleotide of the herpes virus polypeptide. Typically, for DNA molecules, control sequences include promoters, and transcriptional and translational stop signals. Typically, at least one control sequence is foreign to the immunogen encoding region (i.e., from a different gene); thus polynucleotide sequences are typically unnatural. The control sequence may be a suitable transcription termination sequence that is recognized by the host cell to terminate transcription, such as a bovine growth hormone terminator. The termination sequence can be operably linked to the 3' end of the polynucleotide encoding the immunogen. Any terminator which is functional in a vertebrate cell can be used. Preferably, each of the immunogen encoding regions is operably linked to the same transcription terminator. The control sequence may also be a suitable leader sequence, i.e., an untranslated region of an mRNA that is important for translation by a vertebrate cell. The leader sequence can be operably linked to the 5' end of the coding region of the immunogen. Any leader sequence that is functional in a vertebrate cell can be used. The term "operatively connected" means such a configuration: wherein the control sequence is placed in an appropriate position relative to the coding sequence of the polynucleotide such that the control sequence directs expression of the coding sequence.

Vector and expression plasmid

The term "expression vector" means a linear or circular DNA molecule comprising a polynucleotide encoding a herpes virus polypeptide operably linked to control sequences that provide for its expression. Suitable DNA plasmid expression vectors are, for example, the standard plasmid eukaryotic gene expression vector pcdna3.1 or derivatives (accession number LT 727011.1) or pCMV6 (accession number AF 239250) and related derivatives. Viral vectors are described in drager SJ, heney jl. Viruses as vaccine vectors for infectious diseases and cancer. Nat Rev microbiol.2010, month 1; 8 (1) 62-73.Doi:10.1038/nrmicro2240. Although a single DNA vaccination against HSV2 has been demonstrated, multiple DNA vaccinations with some truncated genes have been previously attempted and postulated to reduce the overall immune response by reducing the amount of plasmid DNA components in individuals. Assuming a linear relationship between the amount of DNA applied and the amount of protein, an immune response is thus obtained. The method of the invention is different, maximizing the quality of the immune response by reconstitution of the pro-fusion complex in VLM, which will over time result in a kinetic transition from the engagement of cellular receptors to triggering of the fusion process via the fusion modulator and the progression of the membrane embedding pro-fusion agent from pre-fusion to post-fusion conformation. The inventors speculate that it is possible that multiple DNA plasmids are transported together into cells in vivo, as demonstrated by in vitro cell fusion assays (Turner et al, 1998), and that virus-like membranes (VLMs) are also formed in variable mixtures in different stages of glycoprotein complex from pre-fusion to post-fusion architecture and transitional states. This may include the gB SNPs as referenced and summarized in Table 4 below, which may stabilize the pre-fusion or fusion constructs. Thus, the multiple expression plasmids may be used for in vivo DNA vaccination, such as a plasmid encoding each herpesvirus polypeptide of a fusogenic complex. Alternatively, expression plasmids expressing more than one herpes virus polypeptide may be used with regulatory signals to allow independent expression.

Suitable RNA polynucleotides may comprise a 5' end cap upstream of the immunogen encoding region, such as 7mG (5 ') ppp (5 ') NlmpNp, and/or may comprise one or more modified bases. Suitable modified bases are selected from pseudouridine, nl-methyl pseudouridine, nl-ethyl pseudouridine, 2-thiouridine, 4 '-thiouridine, 5-methylcytosine, 2-thio-l-methyl-1-deaza-pseudouridine, 2-thio-l-methyl-pseudouridine, 2-thio-5-aza-uridine, 2-thio-dihydro-pseudouridine, 2-thio-dihydro-uridine, 2-thio-pseudouridine, 4-methoxy-pseudouridine, 4-thio-l-methyl-pseudouridine, 4-thio-pseudouridine, 5-aza-uridine, dihydro-pseudouridine, 5-methoxy-uridine and 2' -0-methyluridine.

Methods of manipulating and synthesizing polynucleotides to generate suitable vectors and expression plasmids are known from Sambrook, j. And d.w. russell,2001 (Molecular Cloning: a laboratory manual, 3 rd edition, cold Spring Harbor Laboratory Press, cold Spring Harbor, N.Y), and synthetic polynucleotides are available from commercial suppliers (e.g., eurofins).

Mutant gB and gD polypeptides

In one embodiment, the gB polypeptide encoded by the immunogenic coding region of gB comprises a mutation that stabilizes the gB polypeptide as a trimer in the fusion conformation, such as a mutation in fusion-related domain I, such as a substitution at a position corresponding to amino acid position 262 of SEQ ID NO 9, such as a substitution wherein the substitution is a non-conservative substitution, such as a less uncharged substitution, such as isoleucine or alanine.

The inventors have identified mutations in gB that appear to stabilize the fusion construct and may contribute to the ability of the fusion-promoting complex to mediate cell fusion in order to increase cell infection in culture. In our previous experiments on human herpesvirus HHV-6A (Tweedy et al, 2017), deep sequencing using next generation sequencing was used to compare the original viral isolate sequences with the passaged viral genome. The results show that gB is the site of one of a few coding changes and that substitution Thr262Ala was identified. This is in fusion-related domain I, which is modeled to increase the stability of the gB trimer of post-fusion constructs, as demonstrated by structural stability changes affecting the free energy value of the construct as shown (Tweedy et al, 2017). This helps the laboratory tissue culture adapt to increased viral transmission as demonstrated by the predominance of the viral population over time. In this virus, the cytopathic effect is a distinct cell fusion, rather than a controlled cell fusion event in HSV1 and HSV 2. As described in the examples, the inventors predicted the corresponding mutation in HSV2 gB using the sequence alignment in fig. 1 and introduced the coding changes while maintaining the codon bias of the virus as described above. The HSV2 mutated gB coding sequence (SEQ ID NO. 17) has the following characteristics: the Kozak sequence is followed by the ATG start codon at positions 1 to 3; at position 784 the A substitution is G (the corresponding codon ACG is changed to GCG, encoding a substitution of Thr to Ala). The HSV2 mutated gB amino acid sequence (SEQ ID NO. 8) has the following characteristics: domain I of amino acids Ala150 to Val358, comprising Thr262Ala amino acid substitution.

As described in Tweedy et al, 2017, in post-fusion constructs there are crystal structures of homologous gB molecules that can be used for HCMV, HSV and EBV. Recent results also describe the pre-fusion constructs of VZV or HSV1gB (Oliver et al 2020, vollmer et al 2020). Structural alignment of the gB polypeptide trimer against any of these trimer reference structures can be obtained by molecular modeling. There are several tools and resources available for retrieving and generating structural alignments. A variety of algorithms can be used to align two or more protein structures, such as distance alignment matrices (Holm and Sander,1998, proteins 33:88-96) or combinatorial extensions (Shindylalov and Bourn, 1998,Protein Engineering 11:739-747). Free energy prediction of gB subunit-subunit interaction stability can be performed using Web server mcms, which predicts stability changes for a wide variety of mutations from graph-based signatures of distance patterns between coding atoms (Pires d.e.v., ascher d.b., blundell t.l.mcms: predicting the effects of mutations in proteins using graph-based signatures.bioinformatics.2014;30:335-342.doi: 10.1093/bioinformation/btt 691). In this way, putative mutations can be modeled to identify those that stabilize the gB polypeptide as a trimer in the post-fusion configuration. If the mutation stabilizes the gB polypeptide as a trimer in the post-fusion configuration, the predicted free energy of subunit-subunit interactions is lower than the free energy of subunit-subunit interactions of the gB polypeptide trimer in the post-fusion configuration (which is identical except for the mutation).

The term "mutation" includes a substitution, insertion or deletion of one or more amino acids, or a combination of substitution, insertion and deletion. Substitution is preferred. Due to the redundancy of the genetic code, a given substitution may be encoded by more than one possible codon. For all substitutions or other mutations, the invention encompasses all encoding nucleic acid molecules encoding the corresponding polypeptide mutations. Typically, suitable mutations can be identified in fusion-related domain I of gB, as this domain can affect the trimer interface. In HSV2, domain I of gB is located in the N-terminal domain region of Ala-150 to Thr-358 (SEQ ID 9). The skilled artisan can identify domain I in herpes viruses by alignment with the amino acid sequence of HSV2, for example by performing multiple alignments with other related human herpes virus sequences, then modeling known defined tertiary constructs in a public domain database (e.g., uniprot), and mapping onto these using publicly available standard tools (Burke and Heldwein, 2015). Examples of multiple contrast software are implemented, for example, by using the Needleman-Wunsch algorithm (Needleman and Wunsch,1970, J.mol. Biol. 48:443-453) as in the Needle program of the EMBOSS package (EMBOSS: the European Molecular Biology Open Software Suite, rice et al, 2000,Trends Genet.16:276-277), preferably in versions 3.0.0 or later. The optional parameters used are a gap opening penalty of 10, a gap expansion penalty of 0.5, and an EBLOSUM62 (the emoss version of BLOSUM 62) substitution matrix. Other suitable software includes MUSCLE ((by log expected multiple sequence comparison, robert C. Edgar, version 3.6, http:// www.drive5.com/MUSCLE; edgar (2004) Nucleic Acids Research (5), 1792-97 and Edgar (2004) BMC Bioinformatics,5 (1): 113), which can be used with default settings as described in the User Guide (3.6, 2005).

With respect to variants of gB, the position is defined relative to the full length native HSV2 polypeptide SEQUENCE of strain HG52 (SEQUENCE ID No. 9). However, the skilled artisan will appreciate that the invention also relates to variants of other HHV gB polypeptides. For clarity, equivalent residues favor mutation for gB other than HSV2 gB of SEQ ID NO. 9. Equivalent positions can be identified by comparing amino acid sequences using pairwise (e.g., clustalW) or multiple (e.g., mulce) alignments. The equivalent position of Thr262 of gB of HSV2 is shown in fig. 1.

In describing the gB or gD variants of the invention, the following nomenclature is applicable for ease of reference. An acceptable IUPAC single letter or three letter amino acid abbreviation is used. The terms "point mutation" and/or "alteration" include deletions, insertions and substitutions. For amino acid substitutions, the following nomenclature is used: original amino acid, position, substituted amino acid. Thus, substitution of threonine at position 262 with alanine is designated "Thr262Ala" or "T262A". For amino acid deletions, the following nomenclature is used: original amino acid, position. Thus, the deletion of threonine at position 262 is designated "Thr262 x" or "T262 x". The insertion may be on the N-side ("upstream", "X-1") or C-side ("downstream", "X+1") of the amino acid occupying a position. For insertion of an amino acid to the C-side ("downstream", "x+1") of the original amino acid ("X"), the following nomenclature is used: original amino acid, position, original amino acid, inserted amino acid. Thus, an alanine insertion following threonine at position 262 is designated "Thr262ThrAla" or "T262TA". In this case, one or more inserted amino acid residues are numbered by adding a lowercase letter to the position number of the amino acid residue preceding the one or more inserted amino acid residues. For insertion of an amino acid to the N-side of the original amino acid (X) ("upstream", "X-1"), the following nomenclature is used: original amino acid, position, inserted amino acid, original amino acid. Thus, the alanine insertion prior to threonine AT position 262 is designated "Thr262AlaThr" or "T262AT". In this case, one or more inserted amino acid residues are numbered by adding an apostrophe lower case letter to the position number of the amino acid residue following the one or more inserted amino acid residues. Variants containing multiple alterations are separated by a plus sign ("+"). Where different alterations may be introduced at one location, the different alterations are separated by commas.

Suitable substitutions may be conservative or non-conservative. As used herein, "conservative" amino acid substitutions refer to substitutions that are made within the same group, and which typically do not substantially affect protein function, such as within the group of basic amino acids (e.g., arginine, lysine, histidine), acidic amino acids (e.g., glutamic acid and aspartic acid), polar amino acids (e.g., glutamine and asparagine), hydrophobic amino acids (e.g., leucine, isoleucine, valine), aromatic amino acids (e.g., phenylalanine, tryptophan, tyrosine), and small amino acids (e.g., glycine, alanine, serine, threonine, methionine). So-called "conservative substitutions" are intended to combine, for example, gly, ala; val, ile, leu; asp, glu; asn, gln; ser, thr; lys, arg; and Phe, tyr. Non-conservative substitutions are not within the above groups.

Suitably, the mutation, which may be a substitution, deletion or insertion, is at a position corresponding to position 262 of SEQ ID NO 9. Substitution at this position is preferred. Suitably, the substitution is non-conservative, such as with isoleucine or alanine. The amino acid sequence or accession number of a representative gB polypeptide is shown together with the amino acid sequence of a suitable variant gB polypeptide comprising a mutation at a position corresponding to position 262 of SEQ ID NO 9 in table 4 below. The location of the mutations and other exemplary mutations are also defined.

Exemplary mutations shown are variant gD or gB nucleotide sequences comprising mutations corresponding to and designed from the initial mutation of a subset of herpesvirus glycoproteins, as disclosed in Montgomery et al, 1996; kadelka et al, 2018; s. et al 2020; burn Aschner et al 2020; oliver et al 2020 and Vollmer et al 2020 and are described herein. These SNPS add features that alter the ADDC performance of gD by limiting HVEM interactions or stabilizing the pre-fusion gB architecture of fusion complexes as described above. The inventors concluded that mutations in the VZV gB structure and disclosed as aligned with HSV1, HCMV and EBV can also be aligned and inferred for HSV2, HHV6A, HHV B, HHV and HHV8 and identify features such as additional cysteine residues in the gB domain I alignment for HCMV, and N-linked glycosylation sites within the gB domain IV beta-30 fold of HHV-6A and HHV-6B, which are not relevant for the alignment (fig. 4). The inventors also inferred, for HSV2 gB, that, from the alignment analysis (fig. 5) and among the reference strain gB genes of HSV1 and VZV and the genetic SNPs designed as indicated in table 4, the pre-fusion stable gB SNPs shown in domain III at 516His to Pro of HSV1 as disclosed by Vollmer et al, 2020 and aligned with VZV gB.

Table 4: gD and gB SNP variants from representative HHV species strains

/>

In embodiments, the immunogenic coding region encoding gB has at least 95% sequence identity, such as at least 97% sequence identity, at least 99% sequence identity, at least 99.5% sequence identity, or 100% sequence identity, to the coding region of a variant gB polypeptide that differs from the native coding region of the corresponding native full-length gB polypeptide only by the codon corresponding to position 262 of SEQ ID NO 9 in the encoded variant gB polypeptide.

In embodiments, gD, gH and gL encoded by the immunogen encoding region have the amino acid sequences of SEQ ID NOs 10, 6 and 7, respectively, and gB encoded by the immunogen encoding region has the amino acid sequence of SEQ ID NO 8 or 9; such as where the gD, gH and gL immunogen encoding regions have the nucleotide sequences of SEQ ID NOs 5, 1 and 2, respectively, or SEQ ID NOs 18, 15 and 16, respectively; and the gB immunogen encoding region has the nucleotide sequence of SEQ ID NO 3, 4 or 17. Here, the mutated gB sequences are SEQ ID NO 3, 17 and 8; and the wild type gB sequences are SEQ ID NOs 4 and 9. In another embodiment, other exemplary SNP mutations in gD or gB as indicated in table 4 may be used in the vaccine composition.

Pharmaceutical composition

The pharmaceutical composition may comprise additional components in addition to one or more nucleic acid molecules. Typically, the herpes virus antigen is provided solely by one or more nucleic acid molecules that express the antigen in vivo, and the pharmaceutical composition itself does not comprise a herpes virus polypeptide antigen. Suitably, one or more nucleic acid molecules encodes an immunomodulatory agent, wherein the one or more nucleic acid molecules is capable of expressing the immunomodulatory agent when introduced into a vertebrate cell; and/or the composition comprises an immunomodulatory agent. Immunomodulators are agents that stimulate an immune response. Suitable immunomodulators or "molecular" adjuvants may be chemokines or cytokines, including viral chemokines. For example, cytokines are useful due to their lymphocyte-regulating properties, such as interleukin-12 (IL-12), GM-CSF, and IL-18. Suitable chemokines include human CCL5 (RANTES), CCL17 (TARC), CCL18 (PARC), CCL20 (mip3α) or CCL19 (mip3β) or CCL2 (MCP-1), CCL22 (MDC), and CXCL13 (BLC) as described in the examples, as disclosed in US 7,384,641 B2 in combination with a DNA vaccine. Suitable viral chemokines may include vmipi (Pawig et al 2015) or a U83 encoded molecule of Kaposi's sarcoma-associated herpesvirus, as described in U.S. Pat. No. 9,850,286B2 and U.S. Pat. No. 8,940,686 B2, including variants of U83A and HHV6 thereof, such as HHV6A. A suitable humanized viral chemokine is iciU83A-N (SEQ ID NOS 135 and 136), also known as "VIT", a viral factor immunotherapeutic agent, as described in the examples and PCT/EP2021/058776,Virokine Therapeutics Ltd, titled "Novel immunomodulator". VIT is a novel cDNA from a newly spliced transcript variant of a parent gene integrated at the human telomere, humanized iciU83A-N, as described by the old HHV-6A genome (Tweedy et al 2016). The so-called "VIT" also includes coding region variants having at least 90%, such as at least 95%, such as 96%, 97%, 98%, 99% or at least 99.5% sequence identity to the iciU83A-N coding sequence as provided in SEQ ID No.135, and the functional domains thereof are described in example 6. The skilled artisan can design and select variants that retain the functional activity of the native VIT (as described in example 6) and have comparable functional activity. The composition may comprise an immunomodulatory agent in the form of a polypeptide, or it may be encoded by a nucleic acid molecule within a gene expression vector such that it will be expressed as a polypeptide in a vertebrate cell along with a herpes virus polypeptide. In other words, it will have appropriate transcriptional and translational control sequences to enable expression of the polypeptide. So-called "VIT" polypeptides also include variants having at least 90%, such as at least 95%, such as 96%, 97%, 98% or at least 99% sequence identity to an iciU83A polypeptide as provided in SEQ ID No.136 as immunomodulators.

The composition may comprise an adjuvant, although it is envisaged that an adjuvant may not be necessary, or may only be required in an amount less than that required to provide the herpes virus polypeptide by means other than the fusogenic complex form, or may only be required to be a less toxic adjuvant. Thus, compositions lacking an adjuvant, such as those containing only chemical adjuvants suitable for human use, such as alum, are also contemplated.

An adjuvant is any substance that is mixed into a composition to increase or otherwise alter the immune response to an antigen. Adjuvants may include, but are not limited to, alK (SO 4) 2, alNa (SO 4) 2, alNH (SO 4) 4, silica, alum, AI (OH) 3, ca3 (PO 4) 2, kaolin, carbon, aluminum hydroxide, muramyl dipeptide, N-acetyl-muramyl-L-threonyl-D-isoglutamine (thr-DMP), N-acetyl-normuramyl-L-alanyl-D-isoglutamine (CGP 11687, also known as nor-MDP), N-acetyl muramyl-L-alanyl-D-isoglutaminyl-L-alanine-2- (1 '2' -dipalmitoyl-s-N-glycerol-3-hydroxyphosphoryloxy) -ethylamine (CGP 19835A, also known as MTP-PE), 2% squalene/Tween-80 (R) emulsion of RIBI (MPL+TDM+CWS), lipopolysaccharide and various derivatives thereof, including lipid A, freund's Complete Adjuvant (FCA), freund's incomplete Adjuvant, merck Adjuvant 65, polynucleotides (e.g., poly IC and poly AU acid), wax D from Mycobacterium tuberculosis (Mycobacterium tuberculosis), substances present in Corynebacterium breve (Corynebacterium parvum), bordetella pertussis (Bordetella pertussis) and members of the genus Brucella (Brucella), liposomes or other lipid emulsions, titermax, ISCOMS, quil A, ALUN (see U.S. Pat. Nos. 58,767 and 5,554,372), lipid A derivatives, cholera toxin derivatives, HSP derivatives, LPS derivatives, synthetic peptide matrices or GMDP, interleukin 1, interleukin 2, montanide ISA-51 and QS-21.

Additional adjuvants or compounds that can be used to alter or stimulate an immune response include ligands for Toll-like receptors (TLRs). In mammals, TLRs are a family of receptors expressed on DCs that recognize and respond to molecular patterns associated with microbial pathogens. Several TLR ligands have been studied extensively as vaccine adjuvants. Bacterial Lipopolysaccharide (LPS) is a TLR4 ligand, and its detoxified variant monophosphoryl lipid a (MPL) is an approved adjuvant for human use. TLR5 is expressed on monocytes and DCs and responds to flagellins, whereas TLR9 recognizes bacterial DNA or other foreign DNA containing CpG motifs. CpG motif containing Oligonucleotides (OLGs) are potent ligands and agonists for TLR9 and their adjuvant properties have been intensively studied. The CpG motifs from the HSV1 and HSV2 genes are naturally higher, which also act as natural ligands for TLR9 to stimulate innate immune signaling, instead of adding exogenous CpG adjuvants.

It is believed that the formation of a fusogenic complex in vivo in the form of a VLM may stimulate an immune response such that no adjuvant is required, or only a lower amount, or only a less toxic adjuvant is required. In vitro expression of fusogenic complexes in vesicle and heterologous viral expression systems has been attempted experimentally and used to study the fusogenic process (Rogalin and Heldwein,2016; vollmer and Grunewald, 2020). However, these are performed in laboratory cell lines used in vitro tissue cultures that may not be composed of lipid formulations (such as epithelial cell targets) in primary specialized cell types in vivo. Expression of glycoprotein genes for fusion complex machinery in vivo would allow for natural lipid formulations inherent to the fusion process. Lipid presentation of the herpesvirus glycoproteins may affect not only complex presentation, glycoprotein complexes may also affect lipid recruitment, such as increased cholesterol in lipid rafts, or affect membrane bending. These lipid associations can also affect the formation of immunogenic extracellular vesicles. HHV gB can associate with these extracellular vesicles (Grabowska et al 2020). Furthermore, in vivo, membrane fusion events can stimulate innate immunity through cell damage sensing via cGAS-STING, TLR7 or TLR9 innate sensing pathways (Holm et al 2012). Furthermore, immune response triggers of certain T cell subsets need to interact with lipids, and this can be facilitated by membrane glycoproteins clustered together in lipid rafts (Adams et al, 2015; birkinshaw et al, 2015). Thus, the purpose of expressing the fusion complex machinery is to mount a response that prevents in vivo transmission and pathology (i.e., intercellular transmission), which is also applicable to therapeutic vaccines.

Suitably, the one or more nucleic acid molecules are provided as supercoiled DNA. Delivery of DNA depends on the construct, with greater delivery being in supercoiled circular DNA (Liu, 2019). Thus, synthesis with highly concentrated formulations maximizes this and enables gene delivery at lower volumes. Suitably, the nucleic acid molecules are aggregated into nanoparticle types with an aggregating agent; this may be particularly useful where the composition comprises more than one nucleic acid molecule. Suitably, the composition comprises bupivacaine or levimasole. These anesthetics have previously been shown to increase expression in preclinical small animal models by single plasmid DNA injection (Pachuk et al, 2000) (Jin et al, 2004). However, this is not used for multiple DNA plasmid injections. The present examples combine bupivacaine with a plurality of DNA plasmids. This also facilitates simultaneous delivery and expression, as it may also have the effect of clustering molecules. Similar methods can use lipid-based nanoparticles to form aggregates (Liu, 2019) that can also be used.

The pharmaceutical composition of the first aspect of the invention is sterile and is typically provided in a sealed sterile container. The term "sterile" includes the following meanings: the nucleic acid molecules have been filtered through a sterile bacterial retention filter (e.g., a 0.2 μm filter) and/or the nucleic acid molecules have been precipitated in a sterile solution (such as 70% ethanol). Any additional components included are also sterile so that the overall composition is sterile. The additional components, if present, may be sterilized with the nucleic acid molecule. The composition is formulated for in vivo delivery (i.e., as a pharmaceutical formulation) without requiring excipients such as DEAE dextran to cross the membrane barrier by disrupting the membrane barrier as in an in vitro formulation. In vivo, this may be toxic, whereas uptake of DNA is typically via intramuscular injection using a sterile needle, or via an inhaler if via the intranasal route, e.g. using a physiological saline solution, into the tissue to maximize uptake by the natural in vivo route, such as phagocytosis by specialized cells present in the tissue or opsonization of muscle cells via bupivacaine.

In an alternative aspect, the sterile pharmaceutical composition is not limited to being provided in a sealed sterile conditioner. All other features related to the pharmaceutical composition of the first aspect may also be applicable to this aspect, including features of its use in medicine.

The one or more nucleic acid molecules may be naked, i.e., unassociated with any protein, adjuvant or other agent that affects the immune system of the recipient. In such cases, it is desirable that one or more polynucleotides be in a physiologically acceptable solution, such as, but not limited to, sterile saline or sterile buffered saline at physiological pH. Alternatively, the polynucleotide may be associated with a polymer or liposome, such as lecithin liposome or other polymer known in the art, as a polynucleotide-liposome mixture, or the polynucleotide may be associated with an adjuvant known in the art to enhance the immune response, or a protein or other carrier. Proteins, if present, are isolated from components with which they may be associated in nature. Agents that aid in uptake of the polynucleotide by the cell, such as, but not limited to, calcium ions, may also be used. These agents are commonly referred to as pharmaceutically acceptable carriers. Microprojectile coating techniques for coating polynucleotides are known in the art and may also be used in conjunction with the present invention. The polynucleotide may be in a pharmaceutically acceptable carrier or buffer solution. Pharmaceutically acceptable carriers or buffer solutions are known in the art and include those described in various texts such as Remington' sPharmaceutical Sciences. The carrier may preferably be a liquid formulation, and preferably is a buffered isotonic aqueous solution. Suitably, the vaccine composition has a physiological or near physiological pH. Suitably, it is physiological or near physiological osmotic pressure and salinity, and/or is endotoxin free. Which may contain sodium chloride and/or sodium acetate. Pharmaceutically acceptable carriers may also include excipients, such as diluents and the like, as well as additives, such as stabilizers, preservatives, solubilizers and the like. As used herein, the term "pharmaceutically acceptable" means approved by the US or EU or other government regulatory agency or listed in the united states pharmacopeia (u.s.pharmacopeia) or other generally recognized pharmacopeia for use in humans.

The pharmaceutical composition of the first aspect of the invention is provided in a sealed sterile container, e.g. in lyophilized, liquid or nebulized form. Suitable sealed sterile containers include sealed sterile containers for needle injections, ampoules, vials, inhalers and the like. Suitably, sealed sterile containers may be used to deliver pharmaceutical compositions, for example, as filled syringes and needles, inhalers, and the like. Suitably, the sealed sterile container may contain a single dose of the pharmaceutical composition.

Infectious agent antigen

In one embodiment, the one or more nucleic acid molecules encode one or more infectious agent antigens, wherein the one or more nucleic acid molecules are capable of expressing the one or more infectious agent antigens when introduced into the vertebrate cell; and/or wherein the pharmaceutical composition further comprises one or more infectious agent antigens. Suitable control sequences that enable expression of one or more infectious agent antigens are as described above with respect to control sequences suitable for expression of a herpes viral polypeptide. For simplicity, it is preferred to provide one or more nucleic acid molecules encoding one or more infectious agent antigens, and polypeptide antigens are therefore preferred.

An "infectious agent antigen" is a molecule derived from an infectious agent, such as by virtue of being encoded in the genome of the infectious agent, which specifically binds to an antibody or to a T Cell Receptor (TCR) that binds to a Major Histocompatibility Complex (MHC) molecule. Antigens that bind antibodies include all classes of molecules and are referred to as B cell antigens. Suitable types of molecules include peptides, polypeptides, glycoproteins, polysaccharides, gangliosides, lipids, phospholipids, DNA, RNA, fragments thereof, portions thereof, and combinations thereof. TCRs bind only peptide fragments of proteins complexed with MHC molecules; the peptide ligand and the native protein from which it is derived are both referred to as T cell antigens. "epitope" refers to an antigenic determinant of a B cell or T cell antigen. Where the B cell epitope is a peptide or polypeptide, it typically comprises three or more amino acids, usually at least 5, more usually at least 8 to 10 amino acids. Amino acids may be adjacent amino acid residues in the primary structure of a polypeptide, or may be spatially juxtaposed in a folded protein. T cell epitopes can be associated with MHC class I or MHC class II molecules. Typically, T cell epitopes that bind to MHC class I are 8 to 11 amino acids in length. Class II molecules may bind peptides of 10 to 30 residues or more in length, with a length of 12 to 16 residues being most preferred. Peptides that bind to a particular allelic form of an MHC molecule contain amino acid residues that allow complementary interactions between the peptide and the allelic MHC molecule. The ability of putative T cell epitopes to bind to MHC molecules can be predicted and confirmed experimentally.

Suitably, the infectious agent antigen comprises a B cell epitope and/or a T cell epitope and suitably comprises a peptide, polypeptide, carbohydrate, lipid, DNA or RNA. Suitable infectious agent antigens may be derived from viruses, bacteria, protozoa, prions, parasites, worms, nematodes or any other potential pathogen. Since the virus-like membrane fusion complex is expressed on the cell surface, a preferred embodiment is that the membrane surface expressed protein acts as a co-expressed antigen from the pathogen. However, this is not exclusive, as other antigens may be presented on MHC class I or II. Examples of viral antigens include coronavirus antigens, such as one or more antigens from SARS-Cov-2 coronavirus; human Immunodeficiency Virus (HIV) antigens such as the products of gag, pol, and env genes, nef proteins, reverse transcriptase, and other HIV components; hepatitis, e.g., hepatitis a, b and c, hepatitis viral antigens such as S, M and L proteins of hepatitis, pre-S antigen of hepatitis b virus, hepatitis c viral RNA; influenza virus antigens hemagglutinin and neuraminidase and other influenza virus antigens; measles virus antigens such as SAG-1 or p30; rubella virus antigens such as proteins El and E2, and other rubella virus components; rotavirus antigens such as VP7sc components and other rotavirus components; respiratory syncytial virus antigens such as RSV fusion protein, M2 protein; or one or more human papilloma virus antigens, such as the L1 protein.

Examples of bacterial antigens include pertussis bacterial antigens such as pertussis toxin; diphtheria bacterial antigens such as diphtheria toxin or erythropolis toxoid (toxoid erythematosis); tetanus bacterial antigens such as tetanus toxin or toxoid; streptococcal bacterial antigens such as M protein and other streptococcal bacterial antigen components. Fungal antigens that may be used include, but are not limited to, candida (Candida) fungal antigen components; histoplasma (histoplasma) fungal antigens, coccidioidomycosis (coccidiodes) fungal antigens such as globular antigens.

The presence of the herpes virus fusogenic complex may cause one or more infectious agent antigens to be delivered to the immune system in a manner that increases their/their immunogenicity. Thus, natural antigens that are not very naturally immunogenic may be used as infectious antigens. In addition, increased immunogenicity may allow for dose savings compared to currently licensed vaccines.

Where the one or more nucleic acid molecules encode one or more infectious agent antigens, the one or more infectious agent antigens may be co-expressed with the herpes virus polypeptide.

Method of manufacture

A corresponding aspect of the invention provides a method of preparing a pharmaceutical composition of the first aspect, the method comprising formulating one or more nucleic acid molecules as defined with respect to the first aspect, together with one or more physiologically acceptable diluents or excipients, into a sterile composition. The formulation may further comprise one or more additional components as discussed in relation to the composition of the first aspect, such as adjuvants and/or immunomodulators. The method may further comprise dispensing the pharmaceutical composition into a sterile container and sealing the sterile container, thereby providing a sterile sealed container.

In vitro VLM and method of manufacture

In a second aspect the invention provides a pharmaceutical composition comprising a plurality of herpes virus polypeptides associated with a lipid membrane, wherein the pharmaceutical composition is formed by expressing the plurality of herpes virus polypeptides in human cells in vitro from one or more nucleic acid molecules comprising a plurality of immunogenic coding regions that collectively encode the plurality of herpes virus polypeptides, wherein each of the plurality of immunogenic coding regions has at least 90% sequence identity to the native coding region of a corresponding native full length herpes virus polypeptide from the same herpes virus species, wherein the plurality of herpes virus polypeptides are:

(ii) gB, gH and gL of the respective associated human herpesviruses.

Suitably, the plurality of herpes virus polypeptides associated with the lipid membrane are provided in the form of membrane vesicles or whole cells. Human cells are used to prepare VLMs for human use to avoid the presence of undesired non-human antigens in the preparation. Suitable human cells include cells derived from membrane vesicles or from the human patient to whom the cells are to be administered.

Suitably, one or more nucleic acid molecules are as defined in relation to the first aspect of the invention. Suitably, the pharmaceutical composition further comprises one or more infectious agent antigens. The characteristics of the infectious agent antigen are as described in relation to the first aspect of the invention. Excipients for delivering cells expressing a gene are typically at physiological pH and salinity in a cell buffer system in sterile solution for delivery by standard infusion of excipients as used for CAR-T cells. Typically, the composition is generally sterile, except for living cells. The pharmaceutical composition may be provided in a sterile, sealed container, such as a drip bag for intravenous infusion into a patient.

The corresponding aspect of the present invention provides a method of preparing a pharmaceutical composition of the second aspect, the method comprising introducing one or more nucleic acid molecules as defined according to the second aspect into a human cell in vitro, thereby allowing the human cell to express a plurality of herpes virus polypeptides from the one or more nucleic acid molecules, thereby obtaining a plurality of herpes virus polypeptides associated with a lipid membrane. The method may further comprise collecting membrane vesicles or whole cells comprising a plurality of herpes virus polypeptides associated with the lipid membrane, and optionally purifying the membrane vesicles or whole cells. The method comprises formulating the pharmaceutical composition with one or more infectious agent antigens, and/or immunomodulators, and/or adjuvants. Features relating to the pharmaceutical composition of the second aspect are also suitable in relation to the method of preparation. Suitable methods for introducing one or more nucleic acid molecules into a cell include transfection as known in the art. Where whole cells are used, the white blood cells may be collected as if CAR-T cells were prepared, and one or more nucleic acid molecules may be introduced instead of the CAR-T gene. Methods for generating CAR-T cells are described in Dotti et al, 2014, and can be adjusted accordingly. Suitable methods for preparing membrane vesicles comprising herpes virus polypeptides are described, for example, in Zeev-Ben-Mortehai et al, 2014. Membrane vesicles may be secreted into the culture medium by transfected cells and purified by methods such as differential centrifugation as described above. Another method for preparing membrane vesicles by engineering cells to express membrane proteins and culturing the cells is described in WO 2015/01478.

Medical use

In another aspect, the invention provides a pharmaceutical composition of the first or second aspect for use in medicine. The pharmaceutical composition of the first aspect of the invention is typically intended for use in animals, typically mammals, typically humans. Although not exclusive, the pharmaceutical composition of the second aspect is primarily intended for use in a human subject.

Herpes virus infection

Suitably, the pharmaceutical composition of the first or second aspect is provided for use in a method of inducing an immune response against a herpes virus; or in a method for preventing or treating a herpes virus infection. In an alternative form, there is provided a method of inducing an immune response to a herpes virus comprising administering to a subject an effective amount of a pharmaceutical composition of the first or second aspect; or a method of preventing or treating a herpes virus infection comprising administering to a subject an effective amount of a pharmaceutical composition of the first or second aspect.

By "inducing an immune response" we include any humoral and/or cellular immune response. Suitably, the immune response comprises an antibody response to one or more herpes virus polypeptides. The antibody titer produced by the pharmaceutical composition of the invention (also referred to herein as a vaccine) can be a neutralizing antibody titer. Antibody titers were determined by enzyme-linked immunosorbent assay (ELISA); and/or by a micro-neutralization assay, e.g., as described (Atanasiu et al, 2018; cairns et al, 2014; cairns et al, 2006; gompels et al, 1991; bourne et al, 2003). Neutralization titers are typically expressed as the highest serum dilution required to achieve a 50% reduction in the number of viral plaque forming units pfu. In some embodiments, an effective amount of vaccine results in a gradual increase in serum neutralizing antibodies to HHV relative to an unimmunized control, such as 2-fold to 200-fold (e.g., 20-fold or 200-fold). For example, the increase in neutralizing antibody titer can be 10-fold to 200-fold, such as about 50-fold, about 100-fold, or about 200-fold, as compared to an unimmunized control.

The efficacy of a vaccine in inducing an immune response to an antigen can be determined using animal experiments, as in preclinical studies (including protection from pathogen attack). For example, mice or guinea pigs can be immunized with a vaccine. After a suitable period of time (e.g., two weeks) to allow immunity to the antigen, the blood sample is tested using ELISA to determine antibody levels, referred to as antibody titers. In some cases, animals are immunized and after an appropriate period of time, challenged with a herpes virus to determine whether protective immunity against the herpes virus has been achieved. Suitable animal tests may be used to develop suitable combinations of herpes virus encoding nucleic acid molecules and other vaccine components (e.g. adjuvants). After exhibiting efficacy in animal models, testing in humans can be considered. Any known immunization method may be used, including formulation of vaccine compositions and selection of dosages, route of administration and schedule of administration (e.g., primary and one or more booster doses) (see, e.g., vaccine: from concept to clinic, paletti and McInnes editions, CRC Press, 1999).

Suitable uses of the vaccine are for the prevention and/or treatment of HHV in humans and other mammals. Pharmaceutical compositions, also referred to herein as vaccines, can be used as therapeutic or prophylactic agents. The vaccines of the present disclosure can be used to provide prophylactic protection against HHV. Although less desirable, vaccines can also be administered to infected individuals to achieve a therapeutic response. The dosage may need to be adjusted accordingly. The vaccine may be administered once, twice, three times, four times or more, but it may be sufficient to administer the vaccine once (optionally followed by a booster). The vaccine may be administered to children (under 18 years) or adults (over 18 years).

Prevention or treatment of HHV can be assessed in animal models. Typically, animals are vaccinated and then challenged with live virus after a period of time has elapsed that allows an immune response to develop. The examples report successful vaccination of guinea pigs with HSV2 polynucleotides and protection from primary genital disease and viral burden following vaginal challenge. Positive effects on reducing recurrent disease and viral shedding (including asymptomatic shedding) were observed, while the latent viral burden was significantly reduced. Thus, preventing HHV infection (e.g., HSV2 or HSV1 infection) according to the present invention may include protecting against acute disease and/or infection; protection against build-up of latent infection; protection against reactivation latency infection and/or viral transmission; and/or to protect against latent viral recurrence and disease. Treatment of HHV infections (e.g., HSV2 or HSV1 infections) may also reduce or protect against established latent infections, reactivation of latent infections, and/or viral transmission, and/or latent viral recurrence and disease. Reactivation of latent infection means that more virus is produced and may be associated with viral transmission even if no disease recurrence (e.g. lesions) is observed. For disease phases occurring after the acute phase of infection, the examples show the particularly advantageous effect of including nucleic acid molecules encoding immunomodulators in vaccine compositions. Immunomodulators can affect the recruitment of immune cells, thereby affecting the control of latency by cellular immunity. Thus, it is preferred that one or more nucleic acid molecules of the composition encode an immunomodulatory agent, wherein the one or more nucleic acid molecules are capable of expressing the immunomodulatory agent when introduced into a vertebrate cell; and/or the composition comprises an immunomodulatory agent. Suitable immunomodulators include chemokines, such as CCL5 or VIT, or other cytokines, as described herein.

Other animal models for testing vaccines for other herpesviruses are known in the art and include disease models of murine, guinea pig and non-human primates, such as neuropathological and genital infections of alpha herpesviruses (HHV 1, HHV2, HHV 3), immunopathology of beta herpesviruses (HHV 5, HHV6A/B, HHV 7) and lymphoproliferation of gamma herpesviruses (HHV 4 and HHV 8) (Belshe et al, 2014; bernstein et al, 2019; bernstein et al, 1999;Dogra and Sparer,2014;Fujiwara and Nakamura,2020; kollias et al, 2015; zerboni et al, 2014). Typically, the prevention or treatment of HHV is directed to HHV of the same species from which the herpesvirus polypeptide is derived. However, cross-protection can be achieved due to the similarity between herpesvirus polypeptides of different species or types. For example, an HSV2 vaccine may protect against HSV1 infection and vice versa.

The actual dosage (i.e., effective amount) of the compositions of the present invention to be administered to an animal or human patient may be determined by physical and physiological factors such as body weight, severity of the condition, type of disease being treated, therapeutic intervention previously or concurrently performed, idiopathic characteristics of the patient, and route of administration. In any event, the practitioner responsible for administration will determine the concentration of one or more active ingredients in the composition and the appropriate dose or doses for the individual subject. In some embodiments, the dosage of polynucleotide or VLM is 1-5 μg, 5-10 μg, 10-15 μg, 15-20 μg, 10-25 μg, 20-50 μg, 30-50 μg, 40-60 μg, 60-80 μg, 60-100 μg, 50-100 μg, 80-120 μg, 40-150 μg, 50-200 μg, 80-200 μg, 100-200 μg, 120-250 μg, 150-250 μg, 180-280 μg, 200-300 μg, 50-300 μg, 80-300 μg, 100-300 μg, 40-300 μg, 50-350 μg, 100-350 μg, 200-350 μg, 320-400 μg, 40-380g, 40-100 μg, 100-400 μg, 200-400 μg or 300-400 μg per dose.

The vaccine may be administered to the subject by intramuscular, intradermal, subcutaneous, intravaginal or intranasal administration, such as by intradermal or intramuscular injection. Embodiments include intravaginal topical application, or intranasal inhalation using an inhaler, or via intranasal application of solution drops containing vaccine formulation. In some embodiments, the administering step comprises contacting the muscle tissue of the subject with a device suitable for injecting the composition. In some embodiments, the administering step comprises contacting the muscle tissue of the subject with a device suitable for injecting the composition in conjunction with electroporation.

Other infections

In the case where the pharmaceutical composition of the first or second aspect comprises an infectious agent antigen, or where the one or more nucleic acid molecules of the pharmaceutical composition of the first aspect encode one or more infectious agent antigens, the pharmaceutical composition may be provided for use in a method of inducing an immune response to the one or more infectious agent antigens; or in a method for preventing or treating an infection caused by an infectious agent, the method comprising one or more infectious agent antigens. In an alternative form, there is provided a method of inducing an immune response to one or more infectious agent antigens, the method comprising administering to a subject (i) an effective amount of a pharmaceutical composition of the first or second aspect comprising one or more infectious agent antigens, or (ii) an effective amount of a pharmaceutical composition of the first aspect, wherein one or more nucleic acid molecules encode one or more infectious agent antigens. In an alternative form, there is provided a method of preventing or treating an infection caused by an infectious agent comprising one or more infectious agent antigens, the method comprising administering to a subject (i) an effective amount of a pharmaceutical composition of the first or second aspect comprising one or more infectious agent antigens, or (ii) an effective amount of a pharmaceutical composition of the first aspect, wherein one or more nucleic acid molecules encode one or more infectious agent antigens.

Considerations regarding identification of induction of immune responses, assessment of prophylaxis or treatment of infection, identification of appropriate dosages and routes of administration are described above with respect to herpes virus vaccination. Similar procedures can be followed for other infections targeted via additional antigens using corresponding preclinical animal models, followed by standard clinical trials as known in the art.

Reference to the literature

Bernstein DI，Earwood JD，Bravo FJ，Cohen GH，Eisenberg RJ，Clark JR，Fairman J，Cardin RD.Vaccine.2011 Mar 3；29(11)：2071-8.doi：10.1016/j.vaccine.2011.01.005.

Epub 2011 lan 14.PMID：21238569.Effects of herpes simplex virus type 2 glycoprotein vaccines and CLDC adjuvant on genital herpes infection in the guinea pig.

Tweedy J，Spyrou MA，Pearson M，Lassner D，Kuhl U，Gompels UA.Viruses.2016 Jan 15；8(1)：19.doi：10.3390/v8010019.PMID：26784220.Complete Genome Sequence of Germline Chromosomally Integrated Human Herpesvirus 6A and Analyses Integration Sites Define a New Human Endogenous Virus with Potential to Reactivate as an Emerging Infection.

Andersson，S.，Davis，D.L.，Dahlback，H.，Jornvall，H.，and Russell，D.W.(1989).Cloning，structure，and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase，a bile acid biosynthetic enzyme.J Biol Chem 264，8222-8229.

Atanasiu，D.，Saw，W.T.，Lazear，E.，Whitbeck，J.C.，Cairns，T.M.，Lou，H.，Eisenberg，R.J.，and Cohen，G.H.(2018).Using Antibodies and Mutants To Localize the Presumptive gH/gL Binding Site on Herpes Simplex Virus gD.J Virol 92.

Athey，J.，Alexaki，A.，Osipova，E.，Rostovtsev，A.，Santana-Quintero，L.V.，Katneni，U.，Simonyan，V.，and Kimchi-Sarfaty，C.(2017).A new and updated resource for codon usage tables.BMC Bioinformatics 18，391.

Beilstein，F.，Cohen，G.H.，Eisenberg，R.J.，Nicolas，V.，Esclatine，A.，and Pasdeloup，D.(2019).Dynamic organization of Herpesvirus glycoproteins on the viral envelope revealed by super-resolution microscopy.PLoS Pathog 15，e1008209.

Belshe，R.B.，Heineman，T.C.，Bernstein，D.I.，Bellamy，A.R.，Ewell，M.，van der Most，R.，and Deal，C.D.(2014).Correlate of immune protection against HSV-1 genital disease in vaccinated women.J Infect Dis 209，828-836.

Belshe，R.B.，Leone，P.A.，Bernstein，D.I.，Wald，A.，Levin，M.J.，Stapleton，J.T.，Gorfinkel，I.，Morrow，R.L.，Ewell，M.G.，Stokes-Riner,A.，et al.(2012).Efficacy results of a trial of a herpes simplex vaccine.N Engl J Med 366，34-43.

Bender，F.C.，Whitbeck，J.C.，Ponce de Leon，M.，Lou，H.，Eisenberg，R.J.，and Cohen，G.H.(2003).Specific association of glycoprotein B with lipid rafts during herpes simplex virus entry.J Virol 77，9542-9552.

Bernstein，D.I.(2020).Use of the guinea pig model of genital herpes to evaluate vaccines and antivirals：review.Antiviral Res，104821.

Bernstein，D.I.，Flechtner，J.B.，McNeil，L.K.，Heineman，T.，Oliphant，T.，Tasker，S.，Wald，A.，Hetherington，S.，and Genocea study，g.(2019).Therapeutic HSV-2 vaccine decreases recurrent virus shedding and recurrent genital herpes disease.Vaccine 37，3443-3450.

Bernstein，D.I.，Tepe，E.R.，Mester，J.C.，Arnold，R.L.，Stanberry，L.R.，and Higgins，T.(1999).Effects of DNA immunization formulated with bupivacaine in murine and guinea pig models of genital herpes simplex virus infection.Vaccine17，1964-1969.

Bourne N，Bravo FJ，Francotte M，Bernstein DI，Myers MG，Slaoui M，Stanberry LR.Herpes simplex virus(HSV)type 2 glycoprotein D subunit vaccines and protection against genital HSV-1 or HSV-2 disease in guinea pigs.J Infect Dis.2003 Feb 15；187(4)：542-9.doi：10.1086/374002.Burke，H.G.，and Heldwein，E.E.(2015).Crystal Structure of the Human Cytomegalovirus Glycoprotein B.PLoS pathog 11，e1005227.

Burn Aschner，C.，Loh，L.N.，Galen，B.，Delwel，I.，Jangra，R.K.，Garforth，S.J.，Chandran，K.，Almo，S.，Jacobs，W.R.，Ware，C.F.，and Herold，B.C.(2020).HVEM signaling promotes protective antibody-dependent cellular cytotoxicity(ADCC)vaccine responses to herpes simplex viruses.Science Immunology 5，eaax2454.

Cairns，T.M.，Ditto，N.T.，Atanasiu，D.，Lou，H.，Brooks，B.D.，Saw，W.T.，Eisenberg，R.J.，and Cohen，G.H.(2019).Surface Plasmon Resonance Reveals Direct Binding of Herpes Simplex Virus Glycoproteins gH/gL to gD and Locates a gH/gL Binding Site on gD.J Virol 93.

Cairns，T.M.，Fontana，J.，Huang，Z.Y.，Whitbeck，J.C.，Atanasiu，D.，Rao，S.，Shelly，S.S.，Lou，H.，Ponce de Leon，M.，Steven，A.C.，et al.(2014).Mechanism of neutralization of herpes simplex virus by antibodies directed at the fusion domain of glycoprotein B.J Virol 88，2677-2689.

Cairns，T.M.，Shaner,M.S.，Zuo，Y.，Ponce-de-Leon，M.，Baribaud，I.，Eisenberg，R.J.，Cohen，G.H.，and Whitbeck，J.C.(2006).Epitope mapping of herpes simplex virus type 2 gH/gL defines distinct antigenic sites，including some associated with biological function.J Virol 80，2596-2608.

Catusse J，Parry CM，Dewin DR，Gompels UA.Inhibition of HIV-1 infection by viral chemokine U83A via high-affinity CCR5 interactions that block human chemokine-induced leukocyte chemotaxis and receptor internalization.Blood.2007 May 1；109(9)：3633-9.doi：10.1182/blood-2006-08-042622.Epub 2007 Jan 5.PMID：17209056

Catusse J，Clark DJ，Gompels UA.2009.CCR5 signalling，but not DARC or D6 regulatory，chemokine receptors are targeted by herpesvirus U83A chemokine which delays receptor internalisation via diversion to a caveolin-linked pathway.J Inflamm.2009 Jul 30；6：22.doi：10.1186/1476-9255-6-22.PMID：19643012

Clark DJ，Catusse J，Stacey A，Borrow P，Gompels UA.2013.Activation of CCR2+human proinflammatory monocytes by human hsrpesvirus-6B chemokine N-terminal peptide.J Gen Virol.2013 Jul；94(Pt 7)：1624-1635.doi：10.1099/vir.0.050153-0.PMID：23535574

Davison，A.J.，Eberle，R.，Ehlers，B.，Hayward，G.S.，McGeoch，D.J.，Minson，A.C.，Pellett，P.E.，Roizman，B.，Studdert，M.J.，and Thiry，E.(2009).The order Herpesvirales.Arch Virol 154，171-177.

Dewin DR，Catusse J，Gompels UA.Identification and characterization of U83A viral chemokine，a broad and potent beta-chemokine agonist for human CCRs with unique selectivity and inhibition by spliced isoform.J Immunol.2006 Jan 1；176(1)：544-56.doi：10.4049/jimmunol.176.1.544.PMID：16365449

Dogra，P.，and Sparer，T.E.(2014).What we have Iearned from animal models of HCMV.Methods Mol Biol 1119，267-288.

Dotti，G.，Gottschalk，S.，Savoldo，B.，and Brenner，M.K.(2014).Design and development of therapies using chimeric antigen receptor-expressing T cells.Immunol Rev 257，107-126.

Eisanberg，R.J.，Atanasiu，D.，Cairns，T.M.，Gallagher，J.R.，Krummenacher，C.，and Cohan，G.H.(2012).Herpes virus fusion and entry：a story with many characters.Viruses 4，800-832.

Fujiwara，S.，and Nakamura，H.(2020).Animal Models for Gammaherpesvirus Infections：Recent Development in the Analysis of Virus-Induced Pathogenesis.Pathogens 9.

Gary，E.N.，and Weiner，D.B.(2020).DNA vaccines：prime time is now.Curr Opin Immunol 65，21-27.

Glaunsinger，B.A.，and Ganem，D.E.(2006).Messenger RNA turnover and its regulation in herpesviral infection.Adv Virus Res 66，337-394.

Gompels，U.A.，Carss，A.L.，Saxby，C.，Hancock，D.C.，Forrester,A.，and Minson，A.C.(1991).Characterization and sequence analyses of antibody-selected antigenic variants of herpes simplex virus show a conformationally complex epitope on glycoprotein H.J Virol 65，2393-2401.

Gompels，U.A.，and Minson，A.C.(1989).Antigenic properties and cellular localization of herpes simplex virus glycoprotein H synthesized in a mammalian cell expression system.J Virol 63，4744-4755.

Grabowska，K.，Wachalska，M.，Graul，M.，Rychlowski，M.，Bienkowska-Szewczyk，K.，and Lipinska，A.D.(2020).Alphaherpesvirus gB Homologs Are Targeted to Extracellular Vesicles，but They Differentially Affect MHC Class II Molecules.Viruses 12.

Grunwald，T.，and Ulbert，S.(2015).Improvement of DNA vaccination by adjuvants and sophisticated delivery devices：vaccine-platforms for the battle against infectious diseases.Clin Exp Vaccine Res 4，1-10.

Hamby，S.E.，and Hirst，J.D.(2008).Prediction of glycosylation sites using random forests.BMC Bioinformatics 9，500.

Hernandez，G.，Osnaya，V.G.，and Perez-Martinez，X.(2019).Conservation and Variability of the AUG Initiation Codon Context in Eukaryotes.Trends Biochem Sci 44，1009-1021.

Hilterbrand，A.T.，and Heldwein，E.E.(2019).Go go gadget glycoprotein！：HSV-1 draws on its sizeable glycoprotein tool kit to customize its diverse entry routes.PLoS Pathog 15，e1007660.

Holm，C.K.，Jensen，S.B.，Jakobsen，M.R.，Cheshenko，N.，Horan，K.A.，Moeller，H.B.，Gonzalez-Dosal，R.，Rasmussen，S.B.，Christensen，M.H.，Yarovinsky，T.O.，et al.(2012).Virus-cell fusion as a trigger of innate immunity dependant on the adaptor STING.Nat Immunol 13，737-743.

Honess，R.W.，Gompels，U.A.，Barrell，B.G.，Craxton，M.，Cameron，K.R.，Staden，R.，Chang，Y.N.，and Hayward，G.S.(1989).Deviations from expected frequencies of CpG dinucleotides in herpesvirus DNAs may be diagnostic of differences in the states of their latent genomes.J Gen Virol 70(Pt 4)，837-855.

Itzhaki RF.Overwhelming Evidence for a Major Role for Herpes Simplex Virus Type 1(HSV1)in Alzheimer′s Disease(AD)；Underwhelming Evidence against.Vaccines(Basel).2021 Jun 21；9(6)：679.doi：10.3390/vaccines9060679.

Jin，H.，Li，Y.，Ma，Z.，Zhang，F.，Xie，Q.，Gu，D.，and Wang，B.(2004).Effect of chemical adjuvants on DNA vaccination.Vaccine 22，2925-2935.

Kadelka，C.，Liechti，T.，Ebner，H.，Schanz，M.，Rusert，P.，Friedrich，N.，Stiegeler，E.，Braun，D.L.，Huber，M.，Scherrer，A.U.，et al.(2018).Distinct IgG1-driven antibody response landscapes demarcate individuals with broadly HIV-1 neutralising activity.J.Exp.Med.215，1589-1608.

Knipe，D.M.，and Howley，P.M.， eds.(2013).Fields Virology，6th edn(Wolters Kluwer).

Kollias，C.M.，Huneke，R.B.，Wigdahl，B.，and Jennings，S.R.(2015).Animal models of herpes simplex virus immunity and pathogenesis.J Neurovirol 21，8-23.

Kowalzik F，Schreiner D，Jensen C，Teschner D，Gehring S，Zepp F.mRNA-Based Vaccines.Vaccines(Basel).2021 Apr 15；9(4)：390.doi：10.3390/vaccines9040390.

Kozak，M.(2005).Regulation of translation via mRNA structure in prokaryotes and eukaryotes.Gene 361，13-37.

Lamb YN.BNT162b2 mRNA CoVID-19 Vaccine：First Approval.Drugs.2021 Mar；81(4)：495-501.doi：10.1007/s40265-021-01480-7.

Lange，P.T.，Lagunoff，M.，and Tarakanova，V.L.(2019).Chewing the Fat：The conserved Abiiity of DNA Viruses to Hijack Cellular Lipid Metabolism.Viruses 11.

Liu，M.A.(2019).A Comparison of Plasmid DNA and mRNA as Vaccine Technologies.Vaccines(Basel)7.

Looker，K.J.，Johnston，C.，Welton，N.J.，James，C.，Vickerman，P.，Turner，K.M.E.，Boily，M.C.，and Gottlieb，S.L.(2020a).The global and regional burden of genital ulcer disease due to herpes simplex virus：a natural history modelling study.BMJ Glob Health 5，e001875.

Looker,K.J.，Magaret，A.S.，May，M.T.，Turner，K.M.E.，Vickerman，P.，Newman，L.M.，and Gottlieb，S.L.(2017).First estimates of the global and regional incidence of neonatal herpes infection.Lancet Glob Health 5，e300-e309.

Looker，K.J.，Welton，N.J.，Sabin，K.M.，Dalal，S.，Vickerman，P.，Turner，K.M.E.，Boily，M.C.，and Gottlieb，S.L.(2020b).Global and regional estimates of the contribution of herpes simplex virus type 2 infection to HIV incidence：a population attributable fraction analysis using published epidemiological data.Lancet Infect Dis 20，240-249.

Milne，R.S.，Mattick，C.，Nicholson，L.，Devaraj，P.，Alcami，A.，and Gompels，U.A.(2000).RANTES binding and down-regulation by a novel human herpesvirus-6 beta chamokine receptor.J Immunol 164，2396-2404.

Minaya，M.A.，Jensen，T.L.，Goll，J.B.，Korom，M.，Datla，S.H.，Belshe，R.B.，and Morrison，L.A.(2017).Molecular Evolution of Herpes Simplex Virus 2 Complete Genomes：Comparison between Primary and Recurrent Infections.J Virol 91.

Montgomery，R.I.，Warner，M.S.，Lum，B.J.，and Spear，P.G.(1996).Herpes simples virus-1 antry into calls mediated by a novel member of the TNF/NGF receptor family.Cell 87，427-436.

Muggeridge，M.I.(2000).Characterization of cell-cell fusion mediated by herpes simplex virus 2 glycoproteins gB，gD，gH and gL in transfected cells.J Gen Virol 81，2017-2027.

Muthumani，K.，Wise，M.C.，Broderick，K.E.，Hutnick，N.，Goodman，J.，Flingai，S.，Yan，J.，Bian，C.B.，Mendoza，J.，Tingey，C.，et al.(2013).HIV-1 Env DNA vaccine plus protein boost delivered by Ep expands B-and T-cell responses and neutralizing phenotype in vivo.PLoS One 8，e84234.

Nugent，T.，and Jones，D.T.(2009).Transmembrane protein topology prediction using support vector machines.BMC Bioinformatics 10.

Oliver，S.L.，Xing，Y.，Chen，D.H.，Roh，S.H.，Pintilie，G.D.，Bushnell，D.A.，Sommer，M.H.，Yang，E.，Carfi，A.，Chiu，W.，and M.，A.A.(2020).A glycoprotein B-neutralizing antibody structure atuncovers a critical domain for herpesvirus fusion initiation..Nat Commun.11，4141.

Pachuk，C.J.，Ciccarelli，R.B.，Samuel，M.，Bayer，M.E.，Troutman，R.D.，Zurawski，D.V.，Schauer，J.I.，Higgins，T.J.，Weiner，D.B.，Sosnoski，D.M.，et al.(2000).

Characterization of a new class of DNA delivery complexes formed by the local anesthetic bupivacaine.Biochim Biophys Acta 1468，20-30.

Patrone，M.，Coroadinha，A.S.，Teixeira，A.P.，and Alves，P.M.(2016).Palmitoylation Strengthens Cholesterol-depandent Multimerization and Fusion Activity of Human Cytomegalovirus Glycoprotein B(gB).JBiol Chem 291，4711-4722.

Lukas Pawig，Christina Klasen，Christian Weber，Jürgen Bernhagen，Heidi Noels Diversity and Inter-Connections in the CXCR4 Chemokine Receptor/Ligand Family：Molecular Perspectives Front Immunol.2015 Aug 21；6：429.doi：10.3389/fimmu.2015.00429.eCollection 2015.PMID：26347749PMCID：PMC4543903 DOI：10.3389/fimmu.2015.00429

Rogalin，H.B.，and Heldwein，E.E.(2016).Characterization of Vesicular Stomatitis Virus Pseudotypes Bearing Essential Entry Glycoproteins gB，gD，gH，and gL of Herpes Simplex Virus 1.J Virol 90，10321-10328.

Rosa SS，Prazeres DMF，Azevedo AM，Marques MPC.mRNA vaccines manufacturing：Challenges and bottlenecks.Vaccine.2021 Apr 15；39(16)：2190-2200.doi：10.1016/j.vaccine.2021.03.038.S.，B.，Gupta，A.，and Ravetch，J.V.(2020).

The role of IgG Fc receptors in antibody-dependent enhancement.Nat Rev Immunol，11.

Stanberry，L.R.，Spruance，S.L.，Cunningham，A.L.，Bernstein，D.I.，Mindel，A.，Sacks，S.，Tyring，S.，Aoki，F.Y.，Slaoui，M.，Denis，M.，et al.(2002).Glycoprotein-D-adjuvant vaccine to prevent genital herpes.N Engl J Med 347，1652-1661.

Strasser，J.E.，Arnold，R.L.，Pachuk，C.，Higgins，T.J.，and Bernstein，D.I.(2000).Herpes simplex virus DNA vaccine efficacy：effect of glycoprotein D plasmid constructs.J Infect Dis 182，1304-1310.

Szpara，M.L.，Gatherer，D.，Ochoa，A.，Greenbaum，B.，Dolan，A.，Bowden，R.J.，Enquist，L.W.，Legendre，M.，and Davison，A.J.(2014).Evolution and diversity in human herpes simplex virus genomes.J Virol 88，1209-1227.

Takata，M.A.，Goncalves-Carneiro，D.，Zang，T.M.，Soll，S.J.，York，A.，Blanco-Melo，D.，and Bieniasz，P.D.(2017).CG dinucleotide suppression enables antiviral defence targeting non-self RNA.Nature 550，124-127.

Thomsen，D.R.，Stenberg，R.M.，Goins，W.F.，and Stinski，M.F.(1984).Promoter-regulatory region of the major immediate early gene of human cytomegalovirus.Proc Natl Acad Sci U S A 81，659-663.

Trujillo，J.A.，Fleming，E.L.，and Perlman，S.(2013).Transgenic CCL2 expression in the central nervous system results in a dysregulated immune response and enhanced lethality after coronavirus infection.J Virol 87，2376-2389.

Turner,A.，Bruun，B.，Minson，T.，and Browne，H.(1998).Glycoproteins gB，gD，and gHgL of herpes simplex virus type 1 are necessary and sufficient to mediate membrane fusion in a Cos cell transfection system.J Virol 72，873-875.

Tweedy J，Spyrou MA，Pearson M，Lassner D，Kuhl U，Gompels UA.Complete Genome Sequence of Germline Chromosomally Integrated Human Herpesvirus 6A and Analyses Integration Sites Define a New Human Endogenous Virus with Potantial to Reactivate as an Emerging Infectioin.Viruses.2016 Jan 15；8(1)：19.doi：10.3390/v8010019.

Tweedy，J.G.，Escriva，E.，Topf，M.，and Gompels，U.A.(2017).Analyses of Tissue Culture Adaptation of Human Herpesvirus-6A by Whole Genome Deep Sequencing Redefines the Reference Sequence and Identifies Virus Entry Complex Changes.Viruses 10.

Verbeke R，Lentacker I，De Smedt SC，Dewitte H.dawn of mRNA vaccines：The COVID-19 case.J Control Release.2021 Mar 30；333：511-520.doi：10.1016/j.jconrel.2021.03.043

Vollmer，B.，and Grunewald，K.(2020).Herpesvirus membrane fusion-a team effort.Curr Opin Struct Biol 62，112-120.

Vollmer，B.，Prazak，V.，Vasishtan，D.，Jefferys，E.E.，Hernandez-Duran，A.，Vallbracht，M.，Klupp，B.G.，Mettenleiter，T.C.，Backovic，M.，Rey，F.A.，Topf，M.and Grunewald，K.(2020)The prefusion structure of herpes simplex virus glycoprotein B.Science Advances 6，eabc1726.

White，E.M.，Stampfer，S.D.，and Heldwein，E.E.(2020).Expression，Purification，and Crystallization of HSV-1 Glycoproteins for Structure Determination.Methods Mol Biol 2060，377-393.

Youssef，S.，Maor，G.，Wildbaum，G.，Grabie，N.，Gour-Lavie，A.，and Karin，N.(2000).C-C chemokine-encoding DNA vaccines enhance breakdown of tolerance to their gene products and treat ongoing adjuvant arthritis.J Clin Invest 106，361-371.

Zeev-Ben-Mordehai，T.，Vasishtan，D.，Siebert，C.A.，Whittle，C.，and Grunewald，K.(2014).Extracellular vesicles：a platform for the structure determination of membrane proteins by Cryo-EM.Structure 22，1687-1692.

Zerboni，L.，Sen，N.，Oliver，S.L.，and Arvin，A.M.(2014).Molecular mechanisms of varicella zoster virus pathogenesis.Nat Rev Microbiol 12，197-210.

The invention is further described by the following examples, which should not be construed as limiting the scope of the invention.

Example 1: computer design and in vitro expression of HSV2 fusion-promoting complexes.

The genes for the "virus-like membrane" were designed in silico and characterized in vitro prior to testing in an in vivo model system. Although the genes necessary and sufficient for HSV cell fusion in vitro have been characterized (Muggeridge, 2000; turner et al, 1998), they have not been tested together in vivo. Instead, the antigenic properties of individual genes or of encoded proteins or of mixtures of proteins are characterized, here in an effort to produce large amounts of proteins-either to increase the yield of the protein as encoded by the gene, or to produce recombinant proteins exogenously. In order to increase the protein yield of genes, DNA immunization is aimed at optimizing expression using delivery devices such as electroporation or nanoparticles, or by improving human codon usage using standard codon usage tables (Liu, 2019). Cell fusion is focused on characterizing the mechanism of cell fusion, which requires crystallization studies of large amounts of proteins in artificial vesicle systems or produced by recombinant viral proteins or by exogenous extracellular vesicles produced by gB overexpression (Rogalin and Heldwein,2016; vollmer and Grunewald,2020; white et al 2020; zeev-Ben-Mortehai et al 2014). Genes with improved codon usage introduced into pathogens have been reported to alter their subsequent folding and functional activity. Previous studies have not focused on functions in cell fusion of genes, but rather on optimizing the production of proteins for antigen stimulation, mainly linear epitopes.

Instead, current findings combine these approaches for antigen and fusion production, and design genes for combined delivery, which would mimic the natural fusion "movement" of viruses as embedded in the cell membrane. It is known that individual viral glycoproteins associate with lipids, e.g., gB and lipid rafts (Bender et al, 2003; lange et al, 2019), and that fusion components aggregate together in a cascade of interactions on membranes, resulting in cell fusion (Beilstein et al, 2019; cairns et al, 2019). Thus, our invention is to express these 4 fusion complex genes together in vivo, which will provide a "virus-like membrane", VLM. This will enable exposure of the transient form of the fusion complex to elicit effective immunity. Furthermore, it may be triggered by a binding event, in which case the native gD binds to its receptor. This binding can also be re-targeted.

To have "motility" of natural wild-type cell fusion, we synthesized wild-type genes all from the same strain. Importantly, reports show that combinations of glycoproteins from different strains may have different activities. Four genes targeted together were gD, gB, gH and gL. Genomic analysis was performed in order to determine and verify their wild type composition. Strains representative in the human population were selected, as reported for HG52, which are also reference strains (Minaya et al, 2017; szpara et al, 2014). All available sequences were compared and analyzed. This was compared to an updated version of the genomic reference strain HG52 of HSV2, as determined by deep sequencing of stock of original isolates using Illumina-based next generation sequencing (NCBI reference sequence: NC_ 001798.2). This reveals some mutations in the previous report of the sequence of the strain and verifies the current gene sequence synthesized. Each gene ORF was linked to the native Kozak consensus sequence. In addition, HSV2 gB was modified to include mutations similar to those described for HHV-6AgB (Twiedy et al, 2017) (FIG. 1).

The coding regions of the genes (including endogenous Kozak sequences) are shown in SEQ ID nos. 15, 16, 17 and 18, encoding gH, gL, mutated gB and gD, respectively. These were synthesized and cloned into expression plasmid pCMV6, with in frame the 5 'promoter from the HCMV IE gene for gene transcription and the 3' polyadenylation site from the SV40 virus for termination. Each gene retains the natural signals for translation, including the Kozak site, the initiation methionine codon, and the stop codon. Each gene retains the natural g+c composition bias and increases CpG bias to trigger the TLR9 innate signaling pathway. Plasmid expression construction was based on a standard pcdna3.1 DNA plasmid expression vector, such as pCMV6neo, which contains the 5' promoter provided by human cytomegalovirus immediate early gene IE1 for gene expression with an RNA transcription start site, kozak consensus sequence as described above, an initiating methionine start codon followed by a terminating stop codon, a polyadenylation site from SV40 virus flanked by restriction enzyme cloning sites. The plasmid also contains a neomycin resistance gene for selection for expression in cells in vitro. The plasmid expression constructs were verified by confirming the in-frame sequences using Sanger and next generation sequencing. The plasmid sizes were as follows: 8338bp (gH 2), 6520bp (gL 2), 7027bp (gD 2) and 8560bp (gB 2).

Their expression was confirmed using in vitro transcriptional translation and transient expression in vitro cell lines. Alternatively, in vitro cell fusion assays may be evaluated following the method of assaying multinucleated cell formation, as described (Muggeridge, 2000; turner et al, 1998). This can be demonstrated by transfection of the HSV VLM gene (including the modified gB gene) along with the EGFP expression plasmid (as expressed by the standard plasmid expression vector pCDNA3.1 and used as a fluorescent marker). Human HEK293 cells were transfected with plasmid expression constructs using commercial transfection reagents (e.g., nanocin plasmid, tecrealtd, or Lipofectamine, invitrogen) and then examined under a fluorescent microscope 48 hours after transfection. Cells receiving EGFP-expressing plasmid emit green fluorescence, wherein the light excitation peak wavelength is 488nm and the emission peak is 509nm. VLM constructs containing EGFP showed significantly increased giant cells relative to EGFP alone, showing cell fusion as measured by cell size (p < 0.001). The addition of the VIT construct to the VLM construct was also similarly increased for cell fusion compared to EGFP alone (p < 0.01). The RNA from the transfected cells was analyzed using standard procedures known to those skilled in the art to determine gene expression from all plasmids. Briefly, oligonucleotide primers or standard commercial primers specific for individual genes were designed from the expression plasmid vector sequences on either side of the inserted gene. RNA was treated with DNase (Invitrogen) to enzymatically remove any remaining transfected plasmid DNA, and then checked for expression using RT-PCR commercial kits (e.g., superscript IV One-Step RT-PCR and Platinum Superfi RT, invitrogen) whether Reverse Transcriptase (RT) is present or not. All transfected cells showed specific expression as indicated by amplification of the cDNA generated from RNA using gene specific oligonucleotide primer pairs only in the presence of RT, while all negative controls with the buffer used remained negative. RNA expression from the expression plasmid is determined by transfection of individual genes in cells and the use of gene expression plasmid DNA constructs of VLM or vlm+vit combinations. These same assays can be used to determine the expression of SNPs in glycoprotein genes and the effect on cell fusion, as in table 4. For example, cell fusion assays can be used to compare the effect of pre-fusion or fusion stabilizing mutations of gB cited in table 4 on pro-fusion complexes.

Example 2: in vitro expression of HSV2 fusion-promoting complex and human chemokine CCL5

To evaluate delivery and related expression of VLM with exogenous genes, VLM genes were co-expressed with human immunomodulator genes. This can be any modulator of immunostimulation, here we select the human chemokine CCL5, which modulates the attractiveness of antigen presentation and effector immune cells critical to the establishment of effective immunity, and is one of the downstream effectors from innate immunostimulants, e.g. via the TLR pathway. This will serve to enhance and concentrate the response. It can also serve as a marker of transgene expression. Strategies such as those similar to the VLM gene were followed. The native gene was determined by evaluating all forms of the gene sequence at NCBI. It was combined with its native Kozak sequence, then DNA was synthesized (SEQ ID 11) and cloned into an expression plasmid as based on the standard DNA plasmid pcdna3.1 as described above. In-frame sequences were also determined by Sanger sequencing and next generation sequencing. The plasmid size was 6121bp. The expression can be verified by in vitro transcriptional translational analysis, as well as by ELISA analysis of the produced protein in transfected cell lines using cDNA analysis and standard methods for detecting CCL5 expression, as described (Human CCL5/RANTES quantikine kit, R & D systems) (Minne et al, 2000).

Example 3: HSV2 DNA vaccines were tested in preclinical in vivo models.

To evaluate the efficacy of the delivered genome component of the "virus-like membrane", preclinical models of infectious diseases were used to test their ability to provide protection as vaccines or immunotherapeutics. This was tested as a prophylactic DNA vaccine formulation in the HSV2 (herpes simplex virus type 2) model of sexually transmitted disease STD. Recent estimates show that this virus affects more than 4 hundred million people worldwide. Lifelong recurrent STD (genital herpes) requires continuous antiviral therapy with toxic drugs, and despite this available small molecule therapy, HSV is an important factor in HIV transmission, which, according to recent analysis, promotes more than 30% of cases (Looker et al 2020 b). Another serious consequence of infection is neonatal disease, where neonatal mortality is high, exceeding 60% (loader et al, 2017) in untreated condition, which is a complication of the main cause of GUD genital ulcer disease, with recent estimates showing an impact on 5% of the world population, about 2 million people (loader et al, 2020 a). Furthermore, complications involving inflammatory effects of HSV recurrence have been proposed, for example in alzheimer's disease, and epidemiological evidence suggests that this effect has potential utility in treating patients with this effect (Itzhaki 2021). Thus, there is a significant unmet medical need for vaccines to prevent infection or disease, however, despite the clinical trials already conducted, no vaccine has been successfully produced so far. Development of prophylactic vaccines would protect discordant partners, neonatal diseases and those affected by HIV. The generation of "virus-like membranes" derived from HSV2 can generate specific immunity against acute viral attack.

There are preclinical small animal models for evaluating the protective efficacy of vaccines against HSV2 disease. These used murine and guinea pig systems. From a regulatory point of view, the guinea pig model is preferred because it mimics the recurrence of STD as occurs in humans, and also shows a correlation that also reflects immune protection in humans (Bernstein, 2020; straser et al, 2000). In addition, efficacy can be compared to the current gold standard of subunit protein vaccines previously used in clinical trials. This consists of the secreted ectodomain of glycoprotein gD from HSV2 formulated with licensed vaccine adjuvants alum and MPL (Belshe et al 2012). The "Herpevac" test evaluates this vaccine against HSV2 in women, and the test results show that against HSV1, but not HSV2 (belshec et al, 2014), the situation becomes complicated by the observed epidemiological changes in genital herpes in the united states, with HSV1 having an increasingly greater role in causing pathology relative to HSV 2. The correlation of protection is neutralizing antibodies, thus this serves as a good comparison for evaluating new vaccines. Indeed, recent and retrospective analysis of this model showed that this vaccine required immune boosting to be effective in humans (Belshe et al, 2014; bernstein,2020; stanberry et al, 2002). This shows that increasing the response can provide protection.

The use of nucleic acid delivery is advantageous over subunit protein vaccines. Subunit protein vaccines have several drawbacks, as recombinantly produced glycoproteins require purification and standardization for administration, and it has stability and toxicity issues when tested. Nucleic acid vaccines, such as those deploying DNA, have excellent advantages due to increased safety, scalability, no need for cold chain, and low production costs. A significant drawback in history is the inability to generate adequate protective immunity in clinical trials. Nevertheless, this delivery has potential because DNA vaccines have been successfully deployed in aquaculture, which use naked DNA plasmid infection to protect salmon from viral disease, and have obtained the license of the european medicines agency (European Medicines Agency) (Liu, 2019). Thus, for human use, it may be effective if the DNA vaccine is able to stimulate an appropriate immune response for protection.

We tested a "virus-like membrane" composed of fusion mechanism genes from HSV2 as described above. In the guinea pig model, we tested a naked DNA plasmid consisting of 4 genes in the plasmid formulation described in example 1 in combination with bupivacaine against HSV 2. The "virus-like membrane" DNA formulation comprises each of the four plasmids (interchangeably referred to as VLM or gD-VLM) in an amount of 50 to 100 μg/100 μl. The "virus-like membrane" DNA with CCL5 had the same formulation, along with 100 μg/100 μl of plasmid DNA (SEQ ID 11) expressing the encoded human chemokine CCL5, as described in example 2. Each DNA combination was formulated with bupivacaine as described (Bernstein et al, 1999; pachuk et al, 2000). The formulation also includes a sterile excipient composed of physiological saline buffered at physiological pH 7. The negative control was vaccine-free, while the positive control was gold standard gD subunit vaccine previously used in the clinical trial as described. This is gD306 (to the outer domain of amino acid 306), a secreted derivative formulated with MPL and alum, which has a similarity to the composition of AS04, AS described in Belshe et al 2012.

The prophylactic preclinical vaccine trial design uses two or three immunizations using a protocol as previously established (Bernstein et al 1999; straser et al 2000). The guinea pig model used herein was immunized by two intramuscular injections, spaced three weeks apart, and then challenged with virus delivered by the intravaginal route. Two dose immunization schedules are the suboptimal regimen used in order to evaluate the degree of protection. This was based on previous experience with only gD-expressing plasmid DNA in a standard guinea pig model (Bernstein, 2020; straser et al, 2000). Higher virus challenge titers than before were also performed later, as well as for test efficacy. Twelve animals per group received either no injection (negative control) or protein subunit vaccine positive control or two test DNA vaccines injected intramuscularly in the hind leg and buttocks, as described (Bernstein et al 1999).

The test was continued, followed by challenge virus inoculation and immunoprotection efficacy assays. Two immunizations were given in 0.1ml volumes, three weeks apart. Viral challenge was then administered to the vaginal fornix three weeks after the final immunization, 1 x 10 ⁶ pfu of HSV-2 strain MS, as described (Bernstein et al, 1999). No adverse events were recorded to any animals after the primary immunization. All animals were then checked daily for acute disease symptoms, i.e. vaginal lesions, from day 3 to day 14 after virus challenge, and the secretory virus titer in the swabs was checked according to the method of Bernstein et al, 1999 (FIG. 2A). The results show that all animals in the negative control group experienced typical vesicular lesions of acute disease. In the positive control group using the gold standard gD protein subunit vaccine with adjuvant MPL/alum, only 25% (3/12) of animals showed disease symptoms. Whereas in the "virus-like membrane" DNA vaccinated group, 0% (0/12) of the animals had any symptoms, indicating complete protection. The group with the combination of "virus-like membrane" DNA together with CCL5 was similar, showing complete protection, with 0/12 animals having any symptoms. The positive control and the two test DNA vaccines showed significant protection compared to the negative control (p <0.01 While "virus-like membrane" DNA vaccines are the best of the same class.

Comparison of the total lesions observed during acute infection over the following fourteen day period also showed significant efficacy of immunization with the "virus-like membrane" (VLM) DNA vaccine compared to the negative control. These showed that lesions were completely eliminated in VLM DNA vaccinated animals. The average total lesion severity score for the animals that did not receive immunization prior to virus challenge (negative control group) was 8.29 (SD 6.57), while the positive control protein subunit vaccine was 0.67 (SD 1.48), as described in the scoring matrix (Bernstein et al, 1999). In contrast, VLM DNA vaccinated animals were free of lesions and fully protected during the total observation period, while VLM DNA plus human chemokine CCL5 vaccinated animals also showed full protection, highly significant compared to negative-to-photograph ratio (p < 0.0001). This is in stark contrast to previous reports of immunization with only gD plasmid DNA in the same guinea pig model. There was incomplete protection giving a total lesion score of 2.7 (+/-0.7) compared to the negative control used herein of 5.9 (+/-0.5) (Bernstein et al, 1999; straser et al, 2000).

Analysis of viral secretion inhibition data supports the above analysis of data that protects against pathology. As shown in fig. 2B, by day 2 post challenge, gD-VLM showed significant protection compared to animals without vaccine, reducing secreted virus titres as detected in vaginal swabs (gD-VLM 3.49log +/-0.4 compared to no vaccine 4.7log +/-0.53, p=0.006), equivalent to efficacy of subunit protein vaccine with adjuvant MPL/alum (similar to formulation tested against HSV1 in patients) (protein subunit vaccine 3.49log +/-0.91). gD-vlm+ccl5 showed similar results (3.2 log +/-0.87, significantly reduced compared to no vaccine, p=0.003). By 8 days post challenge, the protein subunit vaccine showed incomplete protection, with 3/12 animals still at 0.92log +/-0.49 detectable mean virus. In contrast, all gD-VLM DNA vaccine treated animals showed complete protection compared to 5/9 animals where no vaccine was detectable at an average log titer of 1.45+/-0.99, 0/10 animals detected virus (0.7 log cutoff), p=0.02.

In summary, VLM DNA vaccines show high protection against HSV2 challenge both pathologically and by viral secretion, which exceeds that exhibited by gD protein subunit vaccines of previous clinical trials. VLM DNA vaccines show complete protection against acute viral challenge and demonstrate the utility of this innovation. This supports the progress of human trial evaluation.

Example 4 in vivo testing of HSV2 DNA vaccine in preclinical models shows the utility of vaccine in preventing disease and viral infection

To further evaluate the utility of the VLM-virus like membrane technology, further assays were performed to evaluate its efficacy in preventing viral infection. The performed test included scoring disease severity as demonstrated in example 3, while tracking plaque titration of vaginal swabs to determine the effect on viral infection following viral challenge following the immunization protocol described in example 3. Efficacy endpoints are the incidence and severity of acute disease, as well as the effect on viral vaginal replication as measured by plaque assay virus titration. Thus, this example represents a further analysis of the experiment performed in example 3.

For different vaccine treatments versus no vaccine, statistics were performed on all in vivo examples using the Graphpad Prism with one-way anova using the multiple comparison test of Dunnett. In the case of non-gaussian distributions, a non-parametric comparison using the Wilcoxon test was used. Significance was noted at P values <0.05 (, <0.01 (, <0.001 ().

4.1 incidence and severity of acute diseases

The DNA formulation gD-VLM (SEQ ID 15, 16, 17, 18) was tested in comparison to the negative control-no vaccine-or positive control-gD protein (secretion gD 306) +mpl/alum adjuvant-similar to formulations used in early clinical trials showing partial protection of HSV2 and HSV1 in females, which is the benchmark of clinical utility (belche et al 2012).

gD-VLM DNA formulations, both alone and in combination with CCL5, showed complete protection over that shown by the positive control for the gD protein MPL/alum. Daily average lesion scores are shown in figure 2A. Further analysis was of the total acute mean lesion scores of individual animals in each test cohort (12 animals, 11 in no vaccine group) as shown in fig. 6A. VLM vaccine treatment has significantly reduced scores, although the differences between vaccine treatments at this sample size have not reached significance.

4.2. Effects on viral vaginal replication

The results of the treatment on the effect of lesion development were compared with the effect on viral shedding during the primary disease. Analysis of significantly reduced vaginal viral load correlated with the disease protection shown, with viral shedding approaching log reduction, as for gD protein formulations, using the suboptimal immunization schedule for the positive control subunit gD protein.

By day 8 after virus challenge, both gD-VLM DNA vaccine formulations significantly reduced viral shedding to undetectable levels p <0.01 for nearly all animals (fig. 6B). The protocol for these titrations is as described (Bernstein et al 1999,2020;Bernstein 2019).

Thus, in combination with the results of examples 3 and 4, the gD-VLM DNA vaccine formulation shows high efficacy in preventing HSV2 acute diseases and infections.

Example 5 in vivo testing of HSV2 DNA vaccine in preclinical models shows the utility of the vaccine in preventing detectable latent infection and as a therapeutic for preventing recurrent persistent infectious disease

Here, the use of a vaccine containing VLM (SEQ ID 15, 16, 17, 18) in the prevention of recurrent disease as well as latent, persistent infections was evaluated. Following two doses of vaccine immunization schedule, the in vivo preclinical model described in example 3 was followed up to 63 days post viral HSV2 challenge. The assays performed included DNA PCR of the vaginal shedding swab, as well as DNA PCR of the Dorsal Root Ganglion (DRG) and spinal cord at the site of latent infection. Efficacy endpoints are effects on recurrent disease, asymptomatic shedding, and latent viral burden. The limit of detection for viral quantification of 0.7log pfu/ml was marked and measured, and the limit of detection for undetectable qPCR below the limit of detection for 0.5log microgram copy DNA/ml. The DNA PCR method is as described (Bernstein et al, 1999).

5.1 Effect on recurrent disease

The effect of vaccine treatment on disease recurrence was analyzed 15 to 63 days after infection challenge. Cumulative daily lesions were plotted and the total average lesion scores for each individual were compared.

This shows that VLM DNA vaccines containing CCL5 can prevent recurrent disease.

Clearly, the addition of chemokine DNA to VLM therapy shows control of recurrent lesions. gD-vlm+ccl5 treatment showed a trend to protect against recurrent lesions compared to no vaccine treatment, p=0.1; and positive control gD subunit protein vaccine P <0.01 (fig. 7A and 7B). In half of animals with disease recurrence, the cumulative lesion days for the group treated with the vlm+ccl5 formulation and the gD protein subunit vaccine formulation were reduced by one third to one half as for this daily measurable lesion scored from 1-4 redness to ulceration as described (Bernstein et al 1999).

At the same time, half of the animals were completely protected from any disease recurrence (6/12 50%) using the gD-VLM/CCL5 formulation, as shown in FIG. 7A.

5.2 Effect on asymptomatic viral shedding

At day 20 post virus challenge, there is evidence that the effect of vaccine treatment on reducing viral shedding was tested after virus reactivation. For this purpose, the DNA load measured by quantitative PCR in vaginal swabs was used as a surrogate for viral secretion. This detected symptomatic shedding as well as asymptomatic shedding, i.e., secreted viruses with no evidence of pathology.

Analysis of recurrent shedding events and total average load for vaccinated animals compared to non-vaccinated animals was completed. While the gD protein subunit vaccine had no effect, the vlm+ccl5 vaccine significantly reduced viral shedding, the total load was almost halved, and the shedding events were reduced by one third, with one quarter of animals having no detectable shedding (fig. 7C and 7D).

5.3 Effect on the latent viral burden

The effects of establishment of latency at dorsal root ganglion and spinal cord sites were determined. At the end of the study, i.e., at day 63 post virus challenge, the DNA presence at these latency sites was quantified using qPCR (Bernstein et al 199). Similar to the trend for viral secretion, analysis of the total average DRG load showed significantly reduced levels of all vaccines compared to no vaccine, with halving the amount of VLM vaccine, P <0.01 (fig. 8A). More than half of animals treated with VLM DNA vaccine were protected from detectable DNA in DRG compared to <20% of animals not receiving vaccine (fig. 8B).

Analysis of the latent DNA detected in the spinal cord showed similar effects, with VLM vaccine significantly reduced latent DNA load in the spinal cord (p < 0.05) and significantly reduced the number of animals in the spinal cord where DNA was detected (fig. 8C and 8D), half of the animals were protected from detectable latency in the spinal cord. However, the effect of gD subunit protein vaccines on these parameters is more modest and has not reached significance for protecting animals from establishing latent infection, as detected by DNA in the spinal cord.

5.4 summary

VLM DNA vaccine formulations are highly effective against primary diseases and viral replication. The VLM DNA vaccine combined with human chemokine CCL5 had an effect on recurrent viral shedding, which was not observed in the protein subunit vaccine. In addition, both primary and recurrent disease were reduced, which was not observed without CCL5, and the detection of the latency burden was also significantly reduced, with more than half of the animals being fully protected. Only one animal in the study died and this in the no-vaccine group, severe infection of the other two animals in the group prevented sample collection. In contrast, VLM DNA vaccines were safe, showing infection and disease protection, without adverse effects (summarized in table 4).

Based on experience with the positive control gD subunit protein vaccine, this is a suboptimal dosing schedule for this model system. Improvements may be found by altering the dosing regimen or other route of delivery using these new VLM formulations. Interestingly, single dose delivery may be possible as VLM formulations give 100% protection from acute disease. In addition, positive control gD subunit protein vaccines have been subjected to clinical trials, showing partial efficacy against HSV1 (Belshe et al 2012, 2014), and the results herein equal or exceeded that, indicating support for clinical utility. Other cytokines or chemokines may also affect recurrence as shown for the combination of VLM and human CCL 5.

Chemokine-provided cell recruitment showed an enhanced effect on relapse. Cellular immunity is known to affect control of viral reactivation and relapse, and chemokines are known to direct recruitment, activation and migration of immune cells. While antibody effects may prevent initial infection and may be stimulated by appropriate antigen presentation as provided by VLM.

The CCL5 chemokine used herein is a human gene tested in a guinea pig model, and thus effects in the human environment may further improve the results. CCL5 has been well characterized in human cell lines and in ex vivo settings. Thus, the protective effect of chemokines combined with VLM vaccines in the human system may be higher. This, combined with the overall efficacy and some clinical effects beyond the positive control, supports further exploration as prophylactic and therapeutic vaccine treatments for HSV2 in a clinical setting, and further demonstrates the utility as two new VLM immunomodulatory treatments in a new type of vaccine formulation to provide effective protection from disease or infection.

TABLE 5

Example 6: VLM with VIT immunomodulators

The gD-VLM DNA vaccine is effective as a prophylactic approach for acute HSV2 infection or disease, and is particularly effective against latent disease recurrence when combined with the chemokine gene CCL 5. Thus, we tested another chemokine to alter cellular immunity to prevent reactivation of latent viruses.

We have identified human chemokines from the human herpesvirus 6A (HHV-6A) genome (herein referred to as iiciHHV-6A) in an endogenous form of human chromosomal integration (Twidy et al 2016). We have found that the splice transcript cDNA of the human iciU83A gene from the iciHHV-6A genome differs from the U83A chemokine transcript from the circulating episomal viral HHV-6A genome, resulting in a novel chemokine referred to herein as a "VIT" or "viral factor immunotherapeutic". In circulating viruses, U83A encodes a chemokine-like molecule that can mediate immune cell chemotaxis with unique specificity via interaction with an array of four specific human chemokine receptors CCR1, CCR4, CCR5 and CCR6 (Catusse et al, 2009; catusse et al, 2007; clark et al, 2013; dewin et al, 2006). This specificity is different from any other chemokine or microbial peptide. The VIT chemokine gene extends to a downstream stop codon and contains an extended truncated product with a unique hydrophobic tag of 8 amino acids, which can increase membrane association and stability compared to spliced virus U83A.

We have previously shown that the encoded N-terminal domain determines the specificity of chemokine receptor interactions. While the C-terminal domain retains signaling, if it is removed, chemokine binding is present, but no signaling, converting the agonist to antagonist activity (Dewin et al, 2006). This can be depicted as the N-terminal 17 amino acid peptide region (Clark et al, 2013). In the VIT molecule, the novel cDNA encodes the complete N-terminal domain representing the defined receptor specificity, but lacks the C-terminal signaling domain, rather than a splice small tag.

U83A gene has N-terminal poly-T-strands, which differ in length in the wild-type HHV-6A and human integrated iciHHV-6A genomes, disrupting gene expression (Tweedy et al 2016). In order to maintain stable gene expression, the poly-T tract is mutated here. This finding fixes the functional form of the gene, encoding the complete signal sequence, so that the mature product can be secreted and introduced here to function.

The reported specificity is derived from the maintained N-terminal domain, including targeting CCR1, 4, 5, 6 and 8 receptors (Catusse et al, 2009; catusse et al, 2007; dewin et al, 2006). This unique combination allows targeting immunosuppressive T-regulatory lymphocytes, in particular via CCR4 and CCR6. Human CCR6 is monospecific for the human chemokine CCL20, thus this extends CCR6 receptor interactions to the differential nature of the VIT molecule. A unique application is the ability to act as antagonists of these receptors. This is because the C-terminal signaling moiety is no longer present. In particular antagonism of CCR4 has been shown to be a novel mechanism for increasing immunity to target antigens by blocking T regulatory lymphocyte recruitment.

The coding sequence for VIT (including the endogenous Kozak sequence) is given in SEQ ID NO.135, and the amino acid sequence for VIT is given in SEQ ID NO. 136. The coding sequence was synthesized and cloned into expression plasmid pCMV6, having in frame the 5 'promoter and start site for gene transcription from the human cytomegalovirus HCMV IE gene, and the 3' polyadenylation site from SV40 virus for transcription termination.

In the experiments described in the previous examples, VIT was tested as an immunomodulator in combination with VLM. The formulations and intramuscular immunization used were as described in the previous examples for VLM in combination with CCL5 formulation. 250 μg of VLM+VIT formulation contained 50 μg of each of the five gene expression plasmids, four VLM and one VIT plasmid.

The results are summarized below.

TABLE 6

The score for the negative control was "-" and is not shown in the table above.

Example 7: suppression of recurrent viruses and diseases with DNA vaccine VLM in combination with VIT immunomodulators

The experimental setup was the same as in the above example with 12 guinea pigs per queue. Here, positive swabs were analyzed by quantitative PCR to evaluate asymptomatic and symptomatic viral shedding recurrence. Almost all animals have detectable levels of reactivating virus, with detected DNA above a threshold of 0.5log copies/microgram DNA.

VLM itself or subunit protein immunization does not affect recurrent shedding.

Immunization with only a combination of VLM and cytokine genes CCL5 or VIT showed a reduction in the total average log copy number of viral DNA shedding (fig. 9A) and a reduction in the number of actual viral shedding occurrences measured from viral DNA (fig. 9B). This can be significantly reduced with VLM and CCL5 combinations, P <0.05, and shows a trend for VLM and VIT combinations as demonstrated by average log copy number per microgram DNA of individual animals (fig. 9a, b).

To analyze the effect on individual shedding events, cumulative daily shedding was evaluated as shown in fig. 9C. The results showed that by one month after viral infection challenge, recurrent viral shedding days were halved for all gD VLM DNA vaccines compared to no vaccine treatment, whereas the gD protein+mpl/alum formulation effectively doubled recurrent shedding days (p=0.018).

However, two months after challenge, only VLM plus cytokine gene formulation (i.e., plus CCL5 or VIT) continued to inhibit viral shedding, now one third, compared to gD protein vaccines. VLM plus cytokine gene formulation CCL5 or VIT continued to show significant inhibition of viral shedding compared to no vaccine treatment, whereas gene formulation of VLM alone had no effect (p=0.04) (fig. 9C).

The effect of immunization on the number of days of recurrent lesions was analyzed. Scoring systems 1-4 included 1-redness, slight swelling to 4-vesicular-ulcerative lesions. Although none of the VLM vaccinated animals showed any vesicular disease, vlm+vit DNA immunization or gD protein immunization alone suppressed recurrent lesion days by more than half (fig. 10A). This is also shown in the analysis of severity of recurrent lesions. Immunization with vlm+vit DNA or gD protein alone significantly reduced recurrent lesions (fig. 10B).

In the analysis of the establishment of latent phase in the dorsal root ganglion, all VLM vaccine formulations were effective to significantly reduce the detected latent DNA load (fig. 11), including the vlm+vit combination (fig. 11).

VLM DNA immunization prevents acute disease, but combining only with the cytokine gene VIT reduces the severity and occurrence of recurrent disease. This is similar to the gD protein.

However, VLM alone plus cytokine gene formulation reduced viral shedding compared to gD formulation protein immunization that showed enhanced viral shedding in contrast to no vaccine treatment.

In summary, all immunizations reduced viral DNA loading at the dorsal root ganglion latency sites. However, vlm+vit DNA formulation alone appears to sufficiently inhibit reactivation of the latency phase, thereby reducing viral shedding and recurrent disease.

Example 8: induction of neutralizing antibodies by VLM vaccine formulations

Clinical trials of MPL/alum as an adjuvant in combination with gD2 subunit proteins have established a protective immune correlation (Belshe et al, 2014). This shows the correlation of protection against HSV-1 infection with increasing concentrations of antibodies in immunized females as part of the prophylactic vaccine evaluation in this previous clinical trial. Stimulation of antibody responses has also been demonstrated in the evaluation of this vaccine using a three dose immunization schedule in a guinea pig model system as used herein (Bourne et al, 2003). VLM DNA vaccines were evaluated using a shorter two dose immunization schedule compared to the gD2 subunit protein of previous clinical trials. Serum was collected prior to virus challenge, and virus neutralization was then determined using two-fold serial dilutions of serum mixed with HSV2 and BHK cell suspensions, followed by plating in medium to determine virus plaque formation as described (Bourne et al 2003). The results show that the level of neutralizing antibodies after immunization with glycoprotein gD2 protein or VLM DNA is higher. These are highest in VLM DNA vaccines, either alone or in combination with the cytokines CCL5 or VIT. All immunizations induced significant levels of antibodies compared to no vaccine treatment (which was below the limit of detection, p < 0.001), as shown in figure 12.

All immunizations induced significantly elevated levels of specific neutralizing antibodies (fig. 12), which appears to be associated with a reduction in the relative effects of acute viral load and disease. However, the different antibody titers did not vary significantly between immunotherapy and VLM itself could prevent acute disease.

By adding the chemokine or chemokine-like genes CCL5 and VIT to an immunization schedule, differences in the effects on recurrent disease can be observed and these products may affect leukocyte recruitment. This may distort the response to cellular immunity known to protect from latency and contribute to the high efficacy of VLM plus cytokine gene formulations in protecting against HSV2 infection and disease.

Sequence listing

<110> Virol treatment Co., ltd

<120> vaccine composition

<130> VIRBM/P78653PC

<150> GB 2107170.9

<151> 2021/5/19

<150> GB 2015984.4

<151> 2020/10/8

<160> 136

<170> BiSSAP 1.3.6

<210> 1

<211> 2517

<212> DNA

<213> herpes simplex virus type 2 (strain HG 52)

<220>

<223> coding region for gH of HSV2 strain HG52

<400> 1

atgggccccg gtctgtgggt ggtgatgggg gtcctggtgg gcgttgccgg gggccatgac 60

acgtactgga cggagcaaat cgacccgtgg tttttgcacg gtctggggtt ggcccgcacg 120

tactggcgcg acacaaacac cgggcgtctg tggttgccca acacccccga cgccagcgac 180

ccccagcgcg gacgcttggc gcccccgggc gaactcaacc tgactacggc atccgtgccc 240

atgcttcggt ggtacgccga gcgcttttgt ttcgtgttgg tcaccacggc cgagtttcct 300

cgggaccccg ggcagctgct ttacatccca aagacctatc tgctcggccg gcctcggaac 360

gcgagcctgc ccgagctccc cgaggcgggg cccacgtccc gtccccccgc cgaggtgacc 420

cagctcaagg gactgtcgca caaccccggc gcctccgcgc tgttgcggtc ccgggcctgg 480

gtaacattcg cggccgcgcc ggaccgcgag gggcttacgt tcccgcgggg agacgacggg 540

gcgaccgaga ggcacccgga cggccgacgc aacgcgccgc ccccggggcc gcccgcgggg 600

acaccgaggc atccgacgac gaacctgagc atcgcgcatc tgcacaacgc atccgtgacc 660

tggctggccg ccaggggcct gctacggact ccgggtcggt acgtgtacct ctccccgtcg 720

gcctcgacgt ggcccgtggg cgtctggacg acgggcgggc tggcgttcgg gtgcgacgcc 780

gcgctcgtgc gcgcgcgata cgggaagggc ttcatggggc tcgtgatatc gatgcgggac 840

agccctccgg ccgagatcat agtggtgcct gcggacaaga ccctcgctcg ggtcggaaat 900

ccgaccgacg aaaacgcccc cgcggtgctc cccgggcctc cggccggccc caggtatcgc 960

gtctttgtcc tgggggcccc gacgcccgcc gacaacggct cggcgctgga cgccctccgg 1020

cgggtggccg gctaccccga ggagagcacg aactacgccc agtatatgtc gcgggcctat 1080

gcggagtttt tgggggagga cccgggctcc ggcacggacg cgcgtccgtc cctgttctgg 1140

cgcctcgcgg ggctgctcgc ctcgtcgggg tttgcgttcg tcaacgcggc ccacgcccac 1200

gacgcgattc gcctctccga cctgctgggc tttttggccc actcgcgcgt gctggccggc 1260

ctggccgccc ggggagcagc gggctgcgcg gccgactcgg tgttcctgaa cgtgtccgtg 1320

ttggacccgg cggcccgcct gcggctggag gcgcgcctcg ggcatctggt ggccgcgatc 1380

ctcgagcgag agcagagcct ggtggcgcac gcgctgggct atcagctggc gttcgtgttg 1440

gacagccccg cggcctatgg cgcggtggcc ccgagcgcgg cccgcctgat cgacgccctg 1500

tacgccgagt ttctcggcgg ccgcgcgcta accgccccga tggtccgccg agcgctgttt 1560

tacgccacgg ccgtcctccg ggcgccgttc ctggcgggcg cgccctcggc cgagcagcgg 1620

gaacgcgccc gccggggcct cctcataacc acggccctgt gtacgtccga cgtcgccgcg 1680

gcgacccacg ccgatctccg ggccgcgcta gccaggaccg accaccagaa aaacctcttc 1740

tggctcccgg accacttttc cccatgcgca gcttccctgc gcttcgatct cgccgagggc 1800

gggttcatcc tggacgcgct ggccatggcc acccgatccg acatcccggc ggacgtcatg 1860

gcacaacaga cccgcggcgt ggcctccgtt ctcacgcgct gggcgcacta caacgccctg 1920

atccgcgcct tcgtcccgga ggccacccac cagtgtagcg gcccgtcgca caacgcggag 1980

ccccggatcc tcgtgcccat cacccacaac gccagctacg tcgtcaccca cacccccttg 2040

ccccgcggga tcggatacaa gcttacgggc gttgacgtcc gccgcccgct gtttatcacc 2100

tatctcaccg ccacctgcga agggcacgcg cgggagattg agccgaagcg gctggtgcgc 2160

accgaaaacc ggcgcgacct cggcctcgtg ggggccgtgt ttctgcgcta caccccggcc 2220

ggggaggtca tgtcggtgct gctggtggac acggatgcca cccaacagca gctggcccag 2280

gggccggtgg cgggcacccc gaacgtgttt tccagcgacg tgccgtccgt ggccctgttg 2340

ttgttcccca acggaactgt gattcatctg ctggcctttg acacgctgcc catcgccacc 2400

atcgcccccg ggtttctggc cgcgtccgcg ctgggggtcg ttatgattac cgcggccctg 2460

gcgggcatcc ttagggtggt ccgaacgtgc gtcccatttt tgtggagacg cgaataa 2517

<210> 2

<211> 675

<212> DNA

<213> herpes simplex virus type 2 (strain HG 52)

<220>

<223> coding region of HG52 glycoprotein gL of HSV strain

<400> 2

atggggttcg tctgtctgtt tgggcttgtc gttatgggag cctggggggc gtggggtggg 60

tcacaggcaa ccgaatatgt tcttcgtagt gttattgcca aagaggtggg ggacatacta 120

agagtgcctt gcatgcggac ccccgcggac gatgtttctt ggcgctacga ggccccgtcc 180

gttattgact atgcccgcat agacggaata tttcttcgct atcactgccc ggggttggac 240

acgtttttgt gggataggca cgcccagagg gcgtatctgg ttaacccctt tctctttgcg 300

gcgggatttt tggaggactt gagtcactct gtgtttccgg ccgacaccca ggaaacaacg 360

acgcgccggg ccctttataa agagatacgc gatgcgttgg gcagtcgaaa acaggccgtc 420

agccacgcac ccgtcagggc cgggtgtgta aactttgact actcacgcac tcgccgctgc 480

gtcgggcgac gcgatttacg gcctgccaac accacgtcaa cgtgggaacc gcctgtgtcg 540

tcggacgatg aagcgagctc gcagtcgaag cccctcgcca cccagccgcc cgtcctcgcc 600

ctttcgaacg cccccccacg gcgggtctcc ccgacgcgag gtcggcgccg gcatactcgc 660

ctccgacgca actag 675

<210> 3

<211> 2715

<212> DNA

<213> artificial sequence

<220>

<223> mutant coding sequence of glycoprotein gB of HSV2 strain HG52

A784G

<400> 3

atgcgcgggg ggggcttgat ttgcgcgctg gtcgtggggg cgctggtggc cgcggtggcg 60

tcggcggccc cggcggcccc ggcggccccc cgcgcctcgg gcggcgtggc cgcgaccgtc 120

gcggcgaacg ggggtcccgc ctcccggccg ccccccgtcc cgagccccgc gaccaccaag 180

gcccggaagc ggaaaaccaa aaagccgccc aagcggcccg aggcgacccc gccccccgac 240

gccaacgcga ccgtcgccgc cggccacgcc acgctgcgcg cgcacctgcg ggaaatcaag 300

gtcgagaacg ccgatgccca gttttacgtg tgcccgcccc cgacgggcgc cacggtggtg 360

cagtttgagc agccgcgccg ctgcccgacg cgcccggagg ggcagaacta cacggagggc 420

atcgcggtgg tcttcaagga gaacatcgcc ccgtacaaat tcaaggccac catgtactac 480

aaagacgtga ccgtgtcgca ggtgtggttc ggccaccgct actcccagtt tatggggata 540

ttcgaggacc gcgcccccgt tcccttcgag gaggtgatcg acaagattaa cgccaagggg 600

gtctgccgct ccacggccaa gtacgtgcgg aacaacatgg agaccaccgc gtttcaccgg 660

gacgaccacg agaccgacat ggagctcaag ccggcgaagg tcgccacgcg cacgagccgg 720

gggtggcaca ccaccgacct caagtacaac ccctcgcggg tggaggcgtt ccatcggtac 780

ggcgcgacgg tcaactgcat cgtcgaggag gtggacgcgc ggtcggtgta cccgtacgat 840

gagtttgtgc tggcgacggg cgactttgtg tacatgtccc cgttttacgg ctaccgggag 900

gggtcgcaca ccgagcacac cagctacgcc gccgaccgct tcaagcaggt cgacggcttc 960

tacgcgcgcg acctcaccac gaaggcccgg gccacgtcgc cgacgacccg caacttgctg 1020

acgaccccca agtttaccgt ggcctgggac tgggtgccga agcgaccggc ggtctgcacc 1080

atgaccaagt ggcaggaggt ggacgagatg ctccgcgccg agtacggcgg ctccttccgc 1140

ttctcctccg acgccatctc gaccaccttc accaccaacc tgaccgagta ctcgctctcg 1200

cgcgtcgacc tgggcgactg catcggccgg gatgcccgcg aggccatcga ccgcatgttt 1260

gcgcgcaagt acaacgccac gcacatcaag gtgggccagc cgcagtacta cctggccacg 1320

gggggcttcc tcatcgcgta ccagcccctc ctcagcaaca cgctcgccga gctgtacgtg 1380

cgggagtaca tgcgggagca ggaccgcaag ccccggaatg ccacgcccgc gccactgcgg 1440

gaggcgccca gcgccaacgc gtccgtggag cgcatcaaga ccacctcctc gatcgagttc 1500

gcccggctgc agtttacgta taaccacata cagcgccacg tgaacgacat gctggggcgc 1560

atcgccgtcg cgtggtgcga gctgcagaac cacgagctga ctctctggaa cgaggcccgc 1620

aagctcaacc ccaacgccat cgcctccgcc accgtcggcc ggcgggtgag cgcgcgcatg 1680

ctcggagacg tcatggccgt ctccacgtgc gtgcccgtcg ccccggacaa cgtgatcgtg 1740

cagaactcga tgcgcgtcag ctcgcggccg gggacgtgct acagccgccc cctggtcagc 1800

tttcggtacg aagaccaggg cccgctgatc gaggggcagc tgggcgagaa caacgagctg 1860

cgcctcaccc gcgacgcgct cgagccgtgc accgtgggcc accggcgcta cttcatcttc 1920

ggcgggggct acgtgtactt cgaggagtac gcgtactctc accagctgag tcgcgccgac 1980

gtcaccaccg tcagcacctt catcgacctg aacatcacca tgctggagga ccacgagttt 2040

gtgcccctgg aggtctacac gcgccacgag atcaaggaca gcggcctgct ggactacacg 2100

gaggtccagc gccgcaacca gctgcacgac ctgcgctttg ccgacatcga cacggtcatc 2160

cgcgccgacg ccaacgccgc catgttcgcg gggctgtgcg cgttcttcga ggggatgggg 2220

gacttggggc gcgcggtcgg caaggtagtc atgggagtag tggggggcgt ggtgtcggcc 2280

gtctcgggcg tgtcctcctt tatgtccaac cccttcgggg cgcttgccgt ggggctgctg 2340

gtcctggccg gcctggtcgc ggccttcttc gccttccgct acgtcctgca actgcaacgc 2400

aatcccatga aggccctgta tccgctcacc accaaggaac tcaagacttc cgaccccggg 2460

ggcgtgggcg gggaggggga ggaaggcgcg gaggggggcg ggtttgacga ggccaagttg 2520

gccgaggccc gagaaatgat ccgatatatg gctttggtgt cggccatgga gcgcacggaa 2580

cacaaggcca gaaagaaggg cacgagcgcc ctgctcagct ccaaggtcac caacatggtt 2640

ctgcgcaagc gcaacaaagc caggtactct ccgctccaca acgaggacga ggccggagac 2700

gaagacgagc tctaa 2715

<210> 4

<211> 2721

<212> DNA

<213> herpes simplex virus type 2 (strain HG 52)

<220>

<223> wild type glycoprotein gB of HSV2 strain HG52 having Kozak sequence

Coding sequence

<400> 4

cccgccatgc gcgggggggg cttgatttgc gcgctggtcg tgggggcgct ggtggccgcg 60

gtggcgtcgg cggccccggc ggccccggcg gccccccgcg cctcgggcgg cgtggccgcg 120

accgtcgcgg cgaacggggg tcccgcctcc cggccgcccc ccgtcccgag ccccgcgacc 180

accaaggccc ggaagcggaa aaccaaaaag ccgcccaagc ggcccgaggc gaccccgccc 240

cccgacgcca acgcgaccgt cgccgccggc cacgccacgc tgcgcgcgca cctgcgggaa 300

atcaaggtcg agaacgccga tgcccagttt tacgtgtgcc cgcccccgac gggcgccacg 360

gtggtgcagt ttgagcagcc gcgccgctgc ccgacgcgcc cggaggggca gaactacacg 420

gagggcatcg cggtggtctt caaggagaac atcgccccgt acaaattcaa ggccaccatg 480

tactacaaag acgtgaccgt gtcgcaggtg tggttcggcc accgctactc ccagtttatg 540

gggatattcg aggaccgcgc ccccgttccc ttcgaggagg tgatcgacaa gattaacgcc 600

aagggggtct gccgctccac ggccaagtac gtgcggaaca acatggagac caccgcgttt 660

caccgggacg accacgagac cgacatggag ctcaagccgg cgaaggtcgc cacgcgcacg 720

agccgggggt ggcacaccac cgacctcaag tacaacccct cgcgggtgga ggcgttccat 780

cggtacggca cgacggtcaa ctgcatcgtc gaggaggtgg acgcgcggtc ggtgtacccg 840

tacgatgagt ttgtgctggc gacgggcgac tttgtgtaca tgtccccgtt ttacggctac 900

cgggaggggt cgcacaccga gcacaccagc tacgccgccg accgcttcaa gcaggtcgac 960

ggcttctacg cgcgcgacct caccacgaag gcccgggcca cgtcgccgac gacccgcaac 1020

ttgctgacga cccccaagtt taccgtggcc tgggactggg tgccgaagcg accggcggtc 1080

tgcaccatga ccaagtggca ggaggtggac gagatgctcc gcgccgagta cggcggctcc 1140

ttccgcttct cctccgacgc catctcgacc accttcacca ccaacctgac cgagtactcg 1200

ctctcgcgcg tcgacctggg cgactgcatc ggccgggatg cccgcgaggc catcgaccgc 1260

atgtttgcgc gcaagtacaa cgccacgcac atcaaggtgg gccagccgca gtactacctg 1320

gccacggggg gcttcctcat cgcgtaccag cccctcctca gcaacacgct cgccgagctg 1380

tacgtgcggg agtacatgcg ggagcaggac cgcaagcccc ggaatgccac gcccgcgcca 1440

ctgcgggagg cgcccagcgc caacgcgtcc gtggagcgca tcaagaccac ctcctcgatc 1500

gagttcgccc ggctgcagtt tacgtataac cacatacagc gccacgtgaa cgacatgctg 1560

gggcgcatcg ccgtcgcgtg gtgcgagctg cagaaccacg agctgactct ctggaacgag 1620

gcccgcaagc tcaaccccaa cgccatcgcc tccgccaccg tcggccggcg ggtgagcgcg 1680

cgcatgctcg gagacgtcat ggccgtctcc acgtgcgtgc ccgtcgcccc ggacaacgtg 1740

atcgtgcaga actcgatgcg cgtcagctcg cggccgggga cgtgctacag ccgccccctg 1800

gtcagctttc ggtacgaaga ccagggcccg ctgatcgagg ggcagctggg cgagaacaac 1860

gagctgcgcc tcacccgcga cgcgctcgag ccgtgcaccg tgggccaccg gcgctacttc 1920

atcttcggcg ggggctacgt gtacttcgag gagtacgcgt actctcacca gctgagtcgc 1980

gccgacgtca ccaccgtcag caccttcatc gacctgaaca tcaccatgct ggaggaccac 2040

gagtttgtgc ccctggaggt ctacacgcgc cacgagatca aggacagcgg cctgctggac 2100

tacacggagg tccagcgccg caaccagctg cacgacctgc gctttgccga catcgacacg 2160

gtcatccgcg ccgacgccaa cgccgccatg ttcgcggggc tgtgcgcgtt cttcgagggg 2220

atgggggact tggggcgcgc ggtcggcaag gtagtcatgg gagtagtggg gggcgtggtg 2280

tcggccgtct cgggcgtgtc ctcctttatg tccaacccct tcggggcgct tgccgtgggg 2340

ctgctggtcc tggccggcct ggtcgcggcc ttcttcgcct tccgctacgt cctgcaactg 2400

caacgcaatc ccatgaaggc cctgtatccg ctcaccacca aggaactcaa gacttccgac 2460

cccgggggcg tgggcgggga gggggaggaa ggcgcggagg ggggcgggtt tgacgaggcc 2520

aagttggccg aggcccgaga aatgatccga tatatggctt tggtgtcggc catggagcgc 2580

acggaacaca aggccagaaa gaagggcacg agcgccctgc tcagctccaa ggtcaccaac 2640

atggttctgc gcaagcgcaa caaagccagg tactctccgc tccacaacga ggacgaggcc 2700

ggagacgaag acgagctcta a 2721

<210> 5

<211> 1182

<212> DNA

<213> herpes simplex virus type 2 (strain HG 52)

<220>

<223> coding sequence for HG52 glycoprotein gD of HSV2 strain

<400> 5

atggggcgtt tgacctccgg cgtcgggacg gcggccctgc tagttgtcgc ggtgggactc 60

cgcgtcgtct gcgccaaata cgccttagca gacccctcgc ttaagatggc cgatcccaat 120

cgatttcgcg ggaagaacct tccggttttg gaccagctga ccgacccccc cggggtgaag 180

cgtgtttacc acattcagcc gagcctggag gacccgttcc agccccccag catcccgatc 240

actgtgtact acgcagtgct ggaacgtgcc tgccgcagcg tgctcctaca tgccccatcg 300

gaggcccccc agatcgtgcg cggggcttcg gacgaggccc gaaagcacac gtacaacctg 360

accatcgcct ggtatcgcat gggagacaat tgcgctatcc ccatcacggt tatggaatac 420

accgagtgcc cctacaacaa gtcgttgggg gtctgcccca tccgaacgca gccccgctgg 480

agctactatg acagctttag cgccgtcagc gaggataacc tgggattcct gatgcacgcc 540

cccgccttcg agaccgcggg tacgtacctg cggctagtga agataaacga ctggacggag 600

atcacacaat ttatcctgga gcaccgggcc cgcgcctcct gcaagtacgc tctccccctg 660

cgcatccccc cggcagcgtg cctcacctcg aaggcctacc aacagggcgt gacggtcgac 720

agcatcggga tgctaccccg ctttatcccc gaaaaccagc gcaccgtcgc cctatacagc 780

ttaaaaatcg ccgggtggca cggccccaag cccccgtaca ccagcaccct gctgccgccg 840

gagctgtccg acaccaccaa cgccacgcaa cccgaactcg ttccggaaga ccccgaggac 900

tcggccctct tagaggatcc cgccgggacg gtgtcttcgc agatcccccc aaactggcac 960

atcccgtcga tccaggacgt cgcgccgcac cacgcccccg ccgcccccag caacccgggc 1020

ctgatcatcg gcgcgctggc cggcagtacc ctggcggtgc tggtcatcgg cggtattgcg 1080

ttttgggtac gccgccgcgc tcagatggcc cccaagcgcc tacgtctccc ccacatccgg 1140

gatgacgacg cgcccccctc gcaccagcca ttgttttact ag 1182

<210> 6

<211> 838

<212> PRT

<213> herpes simplex virus type 2 (strain HG 52)

<220>

<223> HSV2 Strain HG52 glycoprotein gH

<400> 6

Met Gly Pro Gly Leu Trp Val Val Met Gly Val Leu Val Gly Val Ala

1 5 10 15

Gly Gly His Asp Thr Tyr Trp Thr Glu Gln Ile Asp Pro Trp Phe Leu

20 25 30

His Gly Leu Gly Leu Ala Arg Thr Tyr Trp Arg Asp Thr Asn Thr Gly

35 40 45

Arg Leu Trp Leu Pro Asn Thr Pro Asp Ala Ser Asp Pro Gln Arg Gly

50 55 60

Arg Leu Ala Pro Pro Gly Glu Leu Asn Leu Thr Thr Ala Ser Val Pro

65 70 75 80

Met Leu Arg Trp Tyr Ala Glu Arg Phe Cys Phe Val Leu Val Thr Thr

85 90 95

Ala Glu Phe Pro Arg Asp Pro Gly Gln Leu Leu Tyr Ile Pro Lys Thr

100 105 110

Tyr Leu Leu Gly Arg Pro Arg Asn Ala Ser Leu Pro Glu Leu Pro Glu

115 120 125

Ala Gly Pro Thr Ser Arg Pro Pro Ala Glu Val Thr Gln Leu Lys Gly

130 135 140

Leu Ser His Asn Pro Gly Ala Ser Ala Leu Leu Arg Ser Arg Ala Trp

145 150 155 160

Val Thr Phe Ala Ala Ala Pro Asp Arg Glu Gly Leu Thr Phe Pro Arg

165 170 175

Gly Asp Asp Gly Ala Thr Glu Arg His Pro Asp Gly Arg Arg Asn Ala

180 185 190

Pro Pro Pro Gly Pro Pro Ala Gly Thr Pro Arg His Pro Thr Thr Asn

195 200 205

Leu Ser Ile Ala His Leu His Asn Ala Ser Val Thr Trp Leu Ala Ala

210 215 220

Arg Gly Leu Leu Arg Thr Pro Gly Arg Tyr Val Tyr Leu Ser Pro Ser

225 230 235 240

Ala Ser Thr Trp Pro Val Gly Val Trp Thr Thr Gly Gly Leu Ala Phe

245 250 255

Gly Cys Asp Ala Ala Leu Val Arg Ala Arg Tyr Gly Lys Gly Phe Met

260 265 270

Gly Leu Val Ile Ser Met Arg Asp Ser Pro Pro Ala Glu Ile Ile Val

275 280 285

Val Pro Ala Asp Lys Thr Leu Ala Arg Val Gly Asn Pro Thr Asp Glu

290 295 300

Asn Ala Pro Ala Val Leu Pro Gly Pro Pro Ala Gly Pro Arg Tyr Arg

305 310 315 320

Val Phe Val Leu Gly Ala Pro Thr Pro Ala Asp Asn Gly Ser Ala Leu

325 330 335

Asp Ala Leu Arg Arg Val Ala Gly Tyr Pro Glu Glu Ser Thr Asn Tyr

340 345 350

Ala Gln Tyr Met Ser Arg Ala Tyr Ala Glu Phe Leu Gly Glu Asp Pro

355 360 365

Gly Ser Gly Thr Asp Ala Arg Pro Ser Leu Phe Trp Arg Leu Ala Gly

370 375 380

Leu Leu Ala Ser Ser Gly Phe Ala Phe Val Asn Ala Ala His Ala His

385 390 395 400

Asp Ala Ile Arg Leu Ser Asp Leu Leu Gly Phe Leu Ala His Ser Arg

405 410 415

Val Leu Ala Gly Leu Ala Ala Arg Gly Ala Ala Gly Cys Ala Ala Asp

420 425 430

Ser Val Phe Leu Asn Val Ser Val Leu Asp Pro Ala Ala Arg Leu Arg

435 440 445

Leu Glu Ala Arg Leu Gly His Leu Val Ala Ala Ile Leu Glu Arg Glu

450 455 460

Gln Ser Leu Val Ala His Ala Leu Gly Tyr Gln Leu Ala Phe Val Leu

465 470 475 480

Asp Ser Pro Ala Ala Tyr Gly Ala Val Ala Pro Ser Ala Ala Arg Leu

485 490 495

Ile Asp Ala Leu Tyr Ala Glu Phe Leu Gly Gly Arg Ala Leu Thr Ala

500 505 510

Pro Met Val Arg Arg Ala Leu Phe Tyr Ala Thr Ala Val Leu Arg Ala

515 520 525

Pro Phe Leu Ala Gly Ala Pro Ser Ala Glu Gln Arg Glu Arg Ala Arg

530 535 540

Arg Gly Leu Leu Ile Thr Thr Ala Leu Cys Thr Ser Asp Val Ala Ala

545 550 555 560

Ala Thr His Ala Asp Leu Arg Ala Ala Leu Ala Arg Thr Asp His Gln

565 570 575

Lys Asn Leu Phe Trp Leu Pro Asp His Phe Ser Pro Cys Ala Ala Ser

580 585 590

Leu Arg Phe Asp Leu Ala Glu Gly Gly Phe Ile Leu Asp Ala Leu Ala

595 600 605

Met Ala Thr Arg Ser Asp Ile Pro Ala Asp Val Met Ala Gln Gln Thr

610 615 620

Arg Gly Val Ala Ser Val Leu Thr Arg Trp Ala His Tyr Asn Ala Leu

625 630 635 640

Ile Arg Ala Phe Val Pro Glu Ala Thr His Gln Cys Ser Gly Pro Ser

645 650 655

His Asn Ala Glu Pro Arg Ile Leu Val Pro Ile Thr His Asn Ala Ser

660 665 670

Tyr Val Val Thr His Thr Pro Leu Pro Arg Gly Ile Gly Tyr Lys Leu

675 680 685

Thr Gly Val Asp Val Arg Arg Pro Leu Phe Ile Thr Tyr Leu Thr Ala

690 695 700

Thr Cys Glu Gly His Ala Arg Glu Ile Glu Pro Lys Arg Leu Val Arg

705 710 715 720

Thr Glu Asn Arg Arg Asp Leu Gly Leu Val Gly Ala Val Phe Leu Arg

725 730 735

Tyr Thr Pro Ala Gly Glu Val Met Ser Val Leu Leu Val Asp Thr Asp

740 745 750

Ala Thr Gln Gln Gln Leu Ala Gln Gly Pro Val Ala Gly Thr Pro Asn

755 760 765

Val Phe Ser Ser Asp Val Pro Ser Val Ala Leu Leu Leu Phe Pro Asn

770 775 780

Gly Thr Val Ile His Leu Leu Ala Phe Asp Thr Leu Pro Ile Ala Thr

785 790 795 800

Ile Ala Pro Gly Phe Leu Ala Ala Ser Ala Leu Gly Val Val Met Ile

805 810 815

Thr Ala Ala Leu Ala Gly Ile Leu Arg Val Val Arg Thr Cys Val Pro

820 825 830

Phe Leu Trp Arg Arg Glu

835

<210> 7

<211> 224

<212> PRT

<213> herpes simplex virus type 2 (strain HG 52)

<220>

<223> HSV2 Strain HG52 glycoprotein gL

<400> 7

Met Gly Phe Val Cys Leu Phe Gly Leu Val Val Met Gly Ala Trp Gly

1 5 10 15

Ala Trp Gly Gly Ser Gln Ala Thr Glu Tyr Val Leu Arg Ser Val Ile

20 25 30

Ala Lys Glu Val Gly Asp Ile Leu Arg Val Pro Cys Met Arg Thr Pro

35 40 45

Ala Asp Asp Val Ser Trp Arg Tyr Glu Ala Pro Ser Val Ile Asp Tyr

50 55 60

Ala Arg Ile Asp Gly Ile Phe Leu Arg Tyr His Cys Pro Gly Leu Asp

65 70 75 80

Thr Phe Leu Trp Asp Arg His Ala Gln Arg Ala Tyr Leu Val Asn Pro

85 90 95

Phe Leu Phe Ala Ala Gly Phe Leu Glu Asp Leu Ser His Ser Val Phe

100 105 110

Pro Ala Asp Thr Gln Glu Thr Thr Thr Arg Arg Ala Leu Tyr Lys Glu

115 120 125

Ile Arg Asp Ala Leu Gly Ser Arg Lys Gln Ala Val Ser His Ala Pro

130 135 140

Val Arg Ala Gly Cys Val Asn Phe Asp Tyr Ser Arg Thr Arg Arg Cys

145 150 155 160

Val Gly Arg Arg Asp Leu Arg Pro Ala Asn Thr Thr Ser Thr Trp Glu

165 170 175

Pro Pro Val Ser Ser Asp Asp Glu Ala Ser Ser Gln Ser Lys Pro Leu

180 185 190

Ala Thr Gln Pro Pro Val Leu Ala Leu Ser Asn Ala Pro Pro Arg Arg

195 200 205

Val Ser Pro Thr Arg Gly Arg Arg Arg His Thr Arg Leu Arg Arg Asn

210 215 220

<210> 8

<211> 904

<212> PRT

<213> artificial sequence

<220>

<223> mutant glycoprotein gB Thr262Ala of HSV2 strain HG52

<220>

<221> Domain

<222> 150..358

<223> Domain I

<400> 8

Met Arg Gly Gly Gly Leu Ile Cys Ala Leu Val Val Gly Ala Leu Val

1 5 10 15

Ala Ala Val Ala Ser Ala Ala Pro Ala Ala Pro Ala Ala Pro Arg Ala

20 25 30

Ser Gly Gly Val Ala Ala Thr Val Ala Ala Asn Gly Gly Pro Ala Ser

35 40 45

Arg Pro Pro Pro Val Pro Ser Pro Ala Thr Thr Lys Ala Arg Lys Arg

50 55 60

Lys Thr Lys Lys Pro Pro Lys Arg Pro Glu Ala Thr Pro Pro Pro Asp

65 70 75 80

Ala Asn Ala Thr Val Ala Ala Gly His Ala Thr Leu Arg Ala His Leu

85 90 95

Arg Glu Ile Lys Val Glu Asn Ala Asp Ala Gln Phe Tyr Val Cys Pro

100 105 110

Pro Pro Thr Gly Ala Thr Val Val Gln Phe Glu Gln Pro Arg Arg Cys

115 120 125

Pro Thr Arg Pro Glu Gly Gln Asn Tyr Thr Glu Gly Ile Ala Val Val

130 135 140

Phe Lys Glu Asn Ile Ala Pro Tyr Lys Phe Lys Ala Thr Met Tyr Tyr

145 150 155 160

Lys Asp Val Thr Val Ser Gln Val Trp Phe Gly His Arg Tyr Ser Gln

165 170 175

Phe Met Gly Ile Phe Glu Asp Arg Ala Pro Val Pro Phe Glu Glu Val

180 185 190

Ile Asp Lys Ile Asn Ala Lys Gly Val Cys Arg Ser Thr Ala Lys Tyr

195 200 205

Val Arg Asn Asn Met Glu Thr Thr Ala Phe His Arg Asp Asp His Glu

210 215 220

Thr Asp Met Glu Leu Lys Pro Ala Lys Val Ala Thr Arg Thr Ser Arg

225 230 235 240

Gly Trp His Thr Thr Asp Leu Lys Tyr Asn Pro Ser Arg Val Glu Ala

245 250 255

Phe His Arg Tyr Gly Ala Thr Val Asn Cys Ile Val Glu Glu Val Asp

260 265 270

Ala Arg Ser Val Tyr Pro Tyr Asp Glu Phe Val Leu Ala Thr Gly Asp

275 280 285

Phe Val Tyr Met Ser Pro Phe Tyr Gly Tyr Arg Glu Gly Ser His Thr

290 295 300

Glu His Thr Ser Tyr Ala Ala Asp Arg Phe Lys Gln Val Asp Gly Phe

305 310 315 320

Tyr Ala Arg Asp Leu Thr Thr Lys Ala Arg Ala Thr Ser Pro Thr Thr

325 330 335

Arg Asn Leu Leu Thr Thr Pro Lys Phe Thr Val Ala Trp Asp Trp Val

340 345 350

Pro Lys Arg Pro Ala Val Cys Thr Met Thr Lys Trp Gln Glu Val Asp

355 360 365

Glu Met Leu Arg Ala Glu Tyr Gly Gly Ser Phe Arg Phe Ser Ser Asp

370 375 380

Ala Ile Ser Thr Thr Phe Thr Thr Asn Leu Thr Glu Tyr Ser Leu Ser

385 390 395 400

Arg Val Asp Leu Gly Asp Cys Ile Gly Arg Asp Ala Arg Glu Ala Ile

405 410 415

Asp Arg Met Phe Ala Arg Lys Tyr Asn Ala Thr His Ile Lys Val Gly

420 425 430

Gln Pro Gln Tyr Tyr Leu Ala Thr Gly Gly Phe Leu Ile Ala Tyr Gln

435 440 445

Pro Leu Leu Ser Asn Thr Leu Ala Glu Leu Tyr Val Arg Glu Tyr Met

450 455 460

Arg Glu Gln Asp Arg Lys Pro Arg Asn Ala Thr Pro Ala Pro Leu Arg

465 470 475 480

Glu Ala Pro Ser Ala Asn Ala Ser Val Glu Arg Ile Lys Thr Thr Ser

485 490 495

Ser Ile Glu Phe Ala Arg Leu Gln Phe Thr Tyr Asn His Ile Gln Arg

500 505 510

His Val Asn Asp Met Leu Gly Arg Ile Ala Val Ala Trp Cys Glu Leu

515 520 525

Gln Asn His Glu Leu Thr Leu Trp Asn Glu Ala Arg Lys Leu Asn Pro

530 535 540

Asn Ala Ile Ala Ser Ala Thr Val Gly Arg Arg Val Ser Ala Arg Met

545 550 555 560

Leu Gly Asp Val Met Ala Val Ser Thr Cys Val Pro Val Ala Pro Asp

565 570 575

Asn Val Ile Val Gln Asn Ser Met Arg Val Ser Ser Arg Pro Gly Thr

580 585 590

Cys Tyr Ser Arg Pro Leu Val Ser Phe Arg Tyr Glu Asp Gln Gly Pro

595 600 605

Leu Ile Glu Gly Gln Leu Gly Glu Asn Asn Glu Leu Arg Leu Thr Arg

610 615 620

Asp Ala Leu Glu Pro Cys Thr Val Gly His Arg Arg Tyr Phe Ile Phe

625 630 635 640

Gly Gly Gly Tyr Val Tyr Phe Glu Glu Tyr Ala Tyr Ser His Gln Leu

645 650 655

Ser Arg Ala Asp Val Thr Thr Val Ser Thr Phe Ile Asp Leu Asn Ile

660 665 670

Thr Met Leu Glu Asp His Glu Phe Val Pro Leu Glu Val Tyr Thr Arg

675 680 685

His Glu Ile Lys Asp Ser Gly Leu Leu Asp Tyr Thr Glu Val Gln Arg

690 695 700

Arg Asn Gln Leu His Asp Leu Arg Phe Ala Asp Ile Asp Thr Val Ile

705 710 715 720

Arg Ala Asp Ala Asn Ala Ala Met Phe Ala Gly Leu Cys Ala Phe Phe

725 730 735

Glu Gly Met Gly Asp Leu Gly Arg Ala Val Gly Lys Val Val Met Gly

740 745 750

Val Val Gly Gly Val Val Ser Ala Val Ser Gly Val Ser Ser Phe Met

755 760 765

Ser Asn Pro Phe Gly Ala Leu Ala Val Gly Leu Leu Val Leu Ala Gly

770 775 780

Leu Val Ala Ala Phe Phe Ala Phe Arg Tyr Val Leu Gln Leu Gln Arg

785 790 795 800

Asn Pro Met Lys Ala Leu Tyr Pro Leu Thr Thr Lys Glu Leu Lys Thr

805 810 815

Ser Asp Pro Gly Gly Val Gly Gly Glu Gly Glu Glu Gly Ala Glu Gly

820 825 830

Gly Gly Phe Asp Glu Ala Lys Leu Ala Glu Ala Arg Glu Met Ile Arg

835 840 845

Tyr Met Ala Leu Val Ser Ala Met Glu Arg Thr Glu His Lys Ala Arg

850 855 860

Lys Lys Gly Thr Ser Ala Leu Leu Ser Ser Lys Val Thr Asn Met Val

865 870 875 880

Leu Arg Lys Arg Asn Lys Ala Arg Tyr Ser Pro Leu His Asn Glu Asp

885 890 895

Glu Ala Gly Asp Glu Asp Glu Leu

900

<210> 9

<211> 904

<212> PRT

<213> herpes simplex virus type 2 (strain HG 52)

<220>

<223> wild-type glycoprotein gB of HSV2 strain HG52

<400> 9

Met Arg Gly Gly Gly Leu Ile Cys Ala Leu Val Val Gly Ala Leu Val

1 5 10 15

Ala Ala Val Ala Ser Ala Ala Pro Ala Ala Pro Ala Ala Pro Arg Ala

20 25 30

Ser Gly Gly Val Ala Ala Thr Val Ala Ala Asn Gly Gly Pro Ala Ser

35 40 45

Arg Pro Pro Pro Val Pro Ser Pro Ala Thr Thr Lys Ala Arg Lys Arg

50 55 60

Lys Thr Lys Lys Pro Pro Lys Arg Pro Glu Ala Thr Pro Pro Pro Asp

65 70 75 80

Ala Asn Ala Thr Val Ala Ala Gly His Ala Thr Leu Arg Ala His Leu

85 90 95

Arg Glu Ile Lys Val Glu Asn Ala Asp Ala Gln Phe Tyr Val Cys Pro

100 105 110

Pro Pro Thr Gly Ala Thr Val Val Gln Phe Glu Gln Pro Arg Arg Cys

115 120 125

Pro Thr Arg Pro Glu Gly Gln Asn Tyr Thr Glu Gly Ile Ala Val Val

130 135 140

Phe Lys Glu Asn Ile Ala Pro Tyr Lys Phe Lys Ala Thr Met Tyr Tyr

145 150 155 160

Lys Asp Val Thr Val Ser Gln Val Trp Phe Gly His Arg Tyr Ser Gln

165 170 175

Phe Met Gly Ile Phe Glu Asp Arg Ala Pro Val Pro Phe Glu Glu Val

180 185 190

Ile Asp Lys Ile Asn Ala Lys Gly Val Cys Arg Ser Thr Ala Lys Tyr

195 200 205

Val Arg Asn Asn Met Glu Thr Thr Ala Phe His Arg Asp Asp His Glu

210 215 220

Thr Asp Met Glu Leu Lys Pro Ala Lys Val Ala Thr Arg Thr Ser Arg

225 230 235 240

Gly Trp His Thr Thr Asp Leu Lys Tyr Asn Pro Ser Arg Val Glu Ala

245 250 255

Phe His Arg Tyr Gly Thr Thr Val Asn Cys Ile Val Glu Glu Val Asp

260 265 270

Ala Arg Ser Val Tyr Pro Tyr Asp Glu Phe Val Leu Ala Thr Gly Asp

275 280 285

Phe Val Tyr Met Ser Pro Phe Tyr Gly Tyr Arg Glu Gly Ser His Thr

290 295 300

Glu His Thr Ser Tyr Ala Ala Asp Arg Phe Lys Gln Val Asp Gly Phe

305 310 315 320

Tyr Ala Arg Asp Leu Thr Thr Lys Ala Arg Ala Thr Ser Pro Thr Thr

325 330 335

Arg Asn Leu Leu Thr Thr Pro Lys Phe Thr Val Ala Trp Asp Trp Val

340 345 350

Pro Lys Arg Pro Ala Val Cys Thr Met Thr Lys Trp Gln Glu Val Asp

355 360 365

Glu Met Leu Arg Ala Glu Tyr Gly Gly Ser Phe Arg Phe Ser Ser Asp

370 375 380

Ala Ile Ser Thr Thr Phe Thr Thr Asn Leu Thr Glu Tyr Ser Leu Ser

385 390 395 400

Arg Val Asp Leu Gly Asp Cys Ile Gly Arg Asp Ala Arg Glu Ala Ile

405 410 415

Asp Arg Met Phe Ala Arg Lys Tyr Asn Ala Thr His Ile Lys Val Gly

420 425 430

Gln Pro Gln Tyr Tyr Leu Ala Thr Gly Gly Phe Leu Ile Ala Tyr Gln

435 440 445

Pro Leu Leu Ser Asn Thr Leu Ala Glu Leu Tyr Val Arg Glu Tyr Met

450 455 460

Arg Glu Gln Asp Arg Lys Pro Arg Asn Ala Thr Pro Ala Pro Leu Arg

465 470 475 480

Glu Ala Pro Ser Ala Asn Ala Ser Val Glu Arg Ile Lys Thr Thr Ser

485 490 495

Ser Ile Glu Phe Ala Arg Leu Gln Phe Thr Tyr Asn His Ile Gln Arg

500 505 510

His Val Asn Asp Met Leu Gly Arg Ile Ala Val Ala Trp Cys Glu Leu

515 520 525

Gln Asn His Glu Leu Thr Leu Trp Asn Glu Ala Arg Lys Leu Asn Pro

530 535 540

Asn Ala Ile Ala Ser Ala Thr Val Gly Arg Arg Val Ser Ala Arg Met

545 550 555 560

Leu Gly Asp Val Met Ala Val Ser Thr Cys Val Pro Val Ala Pro Asp

565 570 575

Asn Val Ile Val Gln Asn Ser Met Arg Val Ser Ser Arg Pro Gly Thr

580 585 590

Cys Tyr Ser Arg Pro Leu Val Ser Phe Arg Tyr Glu Asp Gln Gly Pro

595 600 605

Leu Ile Glu Gly Gln Leu Gly Glu Asn Asn Glu Leu Arg Leu Thr Arg

610 615 620

Asp Ala Leu Glu Pro Cys Thr Val Gly His Arg Arg Tyr Phe Ile Phe

625 630 635 640

Gly Gly Gly Tyr Val Tyr Phe Glu Glu Tyr Ala Tyr Ser His Gln Leu

645 650 655

Ser Arg Ala Asp Val Thr Thr Val Ser Thr Phe Ile Asp Leu Asn Ile

660 665 670

Thr Met Leu Glu Asp His Glu Phe Val Pro Leu Glu Val Tyr Thr Arg

675 680 685

His Glu Ile Lys Asp Ser Gly Leu Leu Asp Tyr Thr Glu Val Gln Arg

690 695 700

Arg Asn Gln Leu His Asp Leu Arg Phe Ala Asp Ile Asp Thr Val Ile

705 710 715 720

Arg Ala Asp Ala Asn Ala Ala Met Phe Ala Gly Leu Cys Ala Phe Phe

725 730 735

Glu Gly Met Gly Asp Leu Gly Arg Ala Val Gly Lys Val Val Met Gly

740 745 750

Val Val Gly Gly Val Val Ser Ala Val Ser Gly Val Ser Ser Phe Met

755 760 765

Ser Asn Pro Phe Gly Ala Leu Ala Val Gly Leu Leu Val Leu Ala Gly

770 775 780

Leu Val Ala Ala Phe Phe Ala Phe Arg Tyr Val Leu Gln Leu Gln Arg

785 790 795 800

Asn Pro Met Lys Ala Leu Tyr Pro Leu Thr Thr Lys Glu Leu Lys Thr

805 810 815

Ser Asp Pro Gly Gly Val Gly Gly Glu Gly Glu Glu Gly Ala Glu Gly

820 825 830

Gly Gly Phe Asp Glu Ala Lys Leu Ala Glu Ala Arg Glu Met Ile Arg

835 840 845

Tyr Met Ala Leu Val Ser Ala Met Glu Arg Thr Glu His Lys Ala Arg

850 855 860

Lys Lys Gly Thr Ser Ala Leu Leu Ser Ser Lys Val Thr Asn Met Val

865 870 875 880

Leu Arg Lys Arg Asn Lys Ala Arg Tyr Ser Pro Leu His Asn Glu Asp

885 890 895

Glu Ala Gly Asp Glu Asp Glu Leu

900

<210> 10

<211> 393

<212> PRT

<213> herpes simplex virus type 2 (strain HG 52)

<220>

<223> HSV2 Strain HG52 glycoprotein gD

<400> 10

Met Gly Arg Leu Thr Ser Gly Val Gly Thr Ala Ala Leu Leu Val Val

1 5 10 15

Ala Val Gly Leu Arg Val Val Cys Ala Lys Tyr Ala Leu Ala Asp Pro

20 25 30

Ser Leu Lys Met Ala Asp Pro Asn Arg Phe Arg Gly Lys Asn Leu Pro

35 40 45

Val Leu Asp Gln Leu Thr Asp Pro Pro Gly Val Lys Arg Val Tyr His

50 55 60

Ile Gln Pro Ser Leu Glu Asp Pro Phe Gln Pro Pro Ser Ile Pro Ile

65 70 75 80

Thr Val Tyr Tyr Ala Val Leu Glu Arg Ala Cys Arg Ser Val Leu Leu

85 90 95

His Ala Pro Ser Glu Ala Pro Gln Ile Val Arg Gly Ala Ser Asp Glu

100 105 110

Ala Arg Lys His Thr Tyr Asn Leu Thr Ile Ala Trp Tyr Arg Met Gly

115 120 125

Asp Asn Cys Ala Ile Pro Ile Thr Val Met Glu Tyr Thr Glu Cys Pro

130 135 140

Tyr Asn Lys Ser Leu Gly Val Cys Pro Ile Arg Thr Gln Pro Arg Trp

145 150 155 160

Ser Tyr Tyr Asp Ser Phe Ser Ala Val Ser Glu Asp Asn Leu Gly Phe

165 170 175

Leu Met His Ala Pro Ala Phe Glu Thr Ala Gly Thr Tyr Leu Arg Leu

180 185 190

Val Lys Ile Asn Asp Trp Thr Glu Ile Thr Gln Phe Ile Leu Glu His

195 200 205

Arg Ala Arg Ala Ser Cys Lys Tyr Ala Leu Pro Leu Arg Ile Pro Pro

210 215 220

Ala Ala Cys Leu Thr Ser Lys Ala Tyr Gln Gln Gly Val Thr Val Asp

225 230 235 240

Ser Ile Gly Met Leu Pro Arg Phe Ile Pro Glu Asn Gln Arg Thr Val

245 250 255

Ala Leu Tyr Ser Leu Lys Ile Ala Gly Trp His Gly Pro Lys Pro Pro

260 265 270

Tyr Thr Ser Thr Leu Leu Pro Pro Glu Leu Ser Asp Thr Thr Asn Ala

275 280 285

Thr Gln Pro Glu Leu Val Pro Glu Asp Pro Glu Asp Ser Ala Leu Leu

290 295 300

Glu Asp Pro Ala Gly Thr Val Ser Ser Gln Ile Pro Pro Asn Trp His

305 310 315 320

Ile Pro Ser Ile Gln Asp Val Ala Pro His His Ala Pro Ala Ala Pro

325 330 335

Ser Asn Pro Gly Leu Ile Ile Gly Ala Leu Ala Gly Ser Thr Leu Ala

340 345 350

Val Leu Val Ile Gly Gly Ile Ala Phe Trp Val Arg Arg Arg Ala Gln

355 360 365

Met Ala Pro Lys Arg Leu Arg Leu Pro His Ile Arg Asp Asp Asp Ala

370 375 380

Pro Pro Ser His Gln Pro Leu Phe Tyr

385 390

<210> 11

<211> 282

<212> DNA

<213> Chile person

<220>

<223> human chemokine CCL5 with endogenous Kozak sequence

<400> 11

ggtaccatga aggtctccgc ggcagccctc gctgtcatcc tcattgctac tgccctctgc 60

gctcctgcat ctgcctcccc atattcctcg gacaccacac cctgctgctt tgcctacatt 120

gcccgcccac tgccccgtgc ccacatcaag gagtatttct acaccagtgg caagtgctcc 180

aacccagcag tcgtctttgt cacccgaaag aaccgccaag tgtgtgccaa cccagagaag 240

aaatgggttc gggagtacat caactctttg gagatgagct ag 282

<210> 12

<211> 1857

<212> DNA

<213> human herpesvirus 6A Strain U1102

<220>

<223> GO variant genes with in-frame sequences starting from

HHV-6B Z29 gO Gene of second methionine codon

<400> 12

atgcttcaca tctcgcgact cggccttttt ctgggccttt tcgcgatagt catgcactcc 60

gttaatctaa taaaatacac gtctgatccc ttagaagctt tcaaaaccgt caaccgccac 120

aattggagcg acgaacaaag agaacatttt tacgacctcc gaaacttata tacaagtttt 180

tgtcagacaa atctatccct cgactgcttc actcaaattt taactaacgt tttctcttgg 240

gacattcgag attcacaatg caagtctgcg gttagcttgt ctccattaca gaatttaccg 300

cggacagaaa tcaaaatagt gctatcctcg acgactgcaa acaaatctat catcgctagc 360

agtttttctc tattttatct tctgtttgcc acactatcta catataccgc agatccgcca 420

tgcgtagagt tactaccatt taaaattctg ggagcacagt tatttgacat aaaactaacc 480

gaagaatcct tgcggatggc aatgagcaaa ttttccaact cgaatctgac acggtcattg 540

acttccttca cgtcaaaaaa cttctttaat tacaccagct ttgtttactt cttgctctat 600

aacacaacat catgcgtccc ttcaaatgat caatatttca aacagtcgcc aaaacctata 660

aatgttacca cttcctttgg acgagccatc gtaaactttg attcgatact aactactaca 720

ccatcatcga cgtcagcgtc tctcacatca ccacatatcc ctagtaccaa cataccaacc 780

ccagcacctc cccccgtaac aaaaaactct acaaaactgc atacagacac cataaaagtt 840

acaccgaaca cacccactat aacaacgcaa acaacggaaa gcatcaaaaa aatagttaaa 900

cgttcagatt ttcctcgacc catgtacacc ccaaccgaca ttccaactct tacaatccgt 960

cttaacgcca ctattaaaac cgaacaaaac accgaaaacc caaaaagtcc accaaaacca 1020

acaaattttg aaaataccac aatcagaatt cccaaaaccc ttgagagcgc tacagcaaca 1080

acaaacgcaa cccaaaagat cgaaagcacc accttcacaa caataggaat caaggaaatt 1140

aacggcaata cctattcttc accaaaaaac tctatttatc ttaagagcaa atcacagcag 1200

agtacaacaa aattcaccga cgccgaacac accactccga ttttaaagtt taccacttgg 1260

caaaacacgg tacgcacata catgagtcac aacacagaag tacaaaacat gaccgacaaa 1320

ttccagagga caaccttgaa atcctcaaac gagctaccta ccattcagac gttgtctgtc 1380

actccaaaac aaaaactacc gtcgaatgta actgccaaaa ctgaagtaca cataactaac 1440

aacgctttac catctagtaa ttcatcatac tcaatcactg aagtcactaa agaggtaaag 1500

catactagaa tgtcagcgtc cactcacgaa cagataaacc acacagaaat agcacaaata 1560

acaccaattc ttaacgctca cacatcggaa aaatcaacta cacctcaacg gtccttcacc 1620

gctgaaacgt tcttaacgac atcttcaaag cctaacatca taacctggtc aaacttacta 1680

acaacaacgc ctaaggaacc attaacgaat acaagtctaa ggtggacaga tcatatcaca 1740

acacagctaa cgactagcaa tagaactcaa tcagccaaac taacaaaagc taacatctcg 1800

tcacaaacga ctaacatcta cccccaaaca atcacgggac gatctacaga ggtttaa 1857

<210> 13

<211> 2316

<212> DNA

<213> human herpesvirus 6B Strain Z29

<220>

<223> variant gO with SNP-containing HHV-6A U1102 GO in frame

<400> 13

atgcatttgg aggtcatcgt ccaaccctat aaaaaaagca aatactattt tagttacaca 60

ttctccttgt acaaattcac tgtggtcaac tcacccgaca tgcttcacat ctcgcgactc 120

ggcctttttc tggccctttt cgcgatagtc atgcactccg ttaatctaat aaaatacaca 180

tctgatccct tagaagcttt caaaaccgtc aaccgccaca attggagcga cgaacaaaga 240

gaacattttt acgacctccg aaacttgtat acaacttttt gtcagagaaa tctatccctc 300

gactgcttca ctcaaatttt aactaacgtt ttctcttgga acattcgaga tttacaatgc 360

aagtctgcgg ttaacttgtc tccattacag aatttaccgc gggcagaaac caaaatagtg 420

ctatcctcaa cagctgcaaa caaatctatc gtcgctagca gtttttctct attttatctt 480

ctgtttgcca cactatctac atataccgca gatccaccat gcgtagagct actaccgttt 540

aaaattctgg gaacacagtt atttgacata aaactgaccg acgaatcctt gcagatggca 600

atcagtaaat tttccaactc gaatctgaca cggtcattga ctccgttcac tcctgaaatc 660

ttctttaatt acaccagctt tgtttacttc ttgctctata acacaacatc atgcatccgt 720

tcaaatgatc aatatttcga acattcgcca aaacctataa atgttaccac ttcctttgga 780

cgagccatcg taaactttca ttcgatactg actacgacgc catcatcgac gccatcatcg 840

acgtcagcgt ctatcacatc accacatatc cctagtacca acacaccaac cccagaacct 900

tcccccgtaa caaaaaactt tacagaactg cagacagaca ccataaaagt tacaccgaac 960

acacccacca taacaacgca aacaacggaa agcatcaaaa aagtagttaa acgttcagat 1020

tttcctcgac cgatgtacac cccgactgac attccaactc ttacaatccg tcgtaacgcc 1080

actattaaaa ccgaacaaaa caccgaaaac cctaccgaaa acccaaaaag tccaccaaaa 1140

ccaacaaatt ttgaaaatac cacaatcaga attcccgaaa cgtttgagag cactacagtg 1200

gcaacaaaca cgactcaaaa gctcgaaagc accaccttcg caacaacaat aggaatcgag 1260

gaaattagcg acaatatcta ttcttcacca aaaaactcta tttatcttaa gagcaaatca 1320

cagcagagca cgacaaaatt caccgacacc gaacacacca ctccgatttt aaagtttacc 1380

acttggcaag acgcggcgcg cacatacatg agccacaaca cggaagtaca aaacatgacc 1440

gaaaatttta ttaaaatttc tcttggagaa acgatgggaa tcacgcctaa agaacccaca 1500

aatcctaccc aacttctcaa cgtaaaaaac caaacagaat acgcaaacga aacccatagc 1560

acagaagtgc agaccgtcaa aaccttcaaa gaggacagat tccagaggac aactttgaaa 1620

tcctcaagcg agccacctac cgttcagacg ttgtctgtca ctccaaaaaa aaaactaccg 1680

tcaaatgtaa ctgccaaaac tgaagtacag gtaactaaca atgctttacc atctagtaat 1740

tcatcacact caatcactaa agtcaccgaa gaaccaaagc aaaatagaat gtcggcgtcc 1800

actcacggag agatcaacca cacagaaata ccacgaatga caccaattct taacgctcac 1860

acatgggaaa aatcgactac acctcaatgg cccttcaccg ctgaaacgtc cttaacgaca 1920

tcttcaaagt ctgccattct aacctggtca aacttactaa caacgccaaa ggaaccatta 1980

acgaatacaa gtctaaggtc gacaaatcat atcacaacac agctaacgac tagcaacaga 2040

actcaatcag ccaaactaac aaaagctcac gtctcgtcac aaacgactaa catctacccc 2100

caaacaatca cggaacgatc tacggacgtt aaaaaaaaaa gttccacaga aagtcgggaa 2160

gctaacaaaa ctctgcctgg aaacgactac cgcgtcaccg ataaaaactc acacaaccat 2220

ccagataacc tcactaccaa agcatactca acccaaaatg caacgcatta cacatacaac 2280

gaacgacacg atttaaacaa cacagatagc acataa 2316

<210> 14

<211> 692

<212> DNA

<213> human herpesvirus 8K 8.1 strain GK18

<220>

<223> HHV 8K 8.1 ORF variant predictive readthrough

<400> 14

atgagttcca cacagattcg cacagaaatc cctgtggcgc tcctaatcct atgcctttgt 60

ctggtggcgt gccatgccaa ttgtcccacg tatcgttcgc atttgggatt ctggcaagag 120

ggttggagtg gacaggttta tcaggactgg ctaggcagga tgaactgttc ctacgagaat 180

atgacggccc tagaggccgt ctccctaaac gggaccagac tagcagctgg atctccgtcg 240

agtgagtatc caaatgtctc cgtatctgtt gaagatacgt ctgcctctgg gtctggagaa 300

gatgcaatag atgaatcggg gtcgggggag gaagagcgtc ccgtgacctc ccacgtgact 360

tttatgacac aaagcgtcca ggccaccaca gaactgaccg atgccttaat atcagccttt 420

tcaggatcat attcatctgg ggaaccatcc aggaccacgc gaattcgcgt atcaccggtc 480

gcagaaaacg gcagaaatag tggtgctagt aaccgcaaaa ccataaaagt aaataaacgt 540

gtttattgtt cacatgataa agagtggtac tctttactgg tttgggggtt gggttgtggc 600

gtggtggctg gtccgcggtt cagtcatcaa cccccgcccg tgttgtcgag gctcctcttc 660

gtcgcctgtt attggcacca ggaggcggtt ta 692

<210> 15

<211> 2523

<212> DNA

<213> herpes simplex virus type 2 (strain HG 52)

<220>

<223> coding region for gH of HSV2 strain HG52 having Kozak site

<400> 15

acgaccatgg gccccggtct gtgggtggtg atgggggtcc tggtgggcgt tgccgggggc 60

catgacacgt actggacgga gcaaatcgac ccgtggtttt tgcacggtct ggggttggcc 120

cgcacgtact ggcgcgacac aaacaccggg cgtctgtggt tgcccaacac ccccgacgcc 180

agcgaccccc agcgcggacg cttggcgccc ccgggcgaac tcaacctgac tacggcatcc 240

gtgcccatgc ttcggtggta cgccgagcgc ttttgtttcg tgttggtcac cacggccgag 300

tttcctcggg accccgggca gctgctttac atcccaaaga cctatctgct cggccggcct 360

cggaacgcga gcctgcccga gctccccgag gcggggccca cgtcccgtcc ccccgccgag 420

gtgacccagc tcaagggact gtcgcacaac cccggcgcct ccgcgctgtt gcggtcccgg 480

gcctgggtaa cattcgcggc cgcgccggac cgcgaggggc ttacgttccc gcggggagac 540

gacggggcga ccgagaggca cccggacggc cgacgcaacg cgccgccccc ggggccgccc 600

gcggggacac cgaggcatcc gacgacgaac ctgagcatcg cgcatctgca caacgcatcc 660

gtgacctggc tggccgccag gggcctgcta cggactccgg gtcggtacgt gtacctctcc 720

ccgtcggcct cgacgtggcc cgtgggcgtc tggacgacgg gcgggctggc gttcgggtgc 780

gacgccgcgc tcgtgcgcgc gcgatacggg aagggcttca tggggctcgt gatatcgatg 840

cgggacagcc ctccggccga gatcatagtg gtgcctgcgg acaagaccct cgctcgggtc 900

ggaaatccga ccgacgaaaa cgcccccgcg gtgctccccg ggcctccggc cggccccagg 960

tatcgcgtct ttgtcctggg ggccccgacg cccgccgaca acggctcggc gctggacgcc 1020

ctccggcggg tggccggcta ccccgaggag agcacgaact acgcccagta tatgtcgcgg 1080

gcctatgcgg agtttttggg ggaggacccg ggctccggca cggacgcgcg tccgtccctg 1140

ttctggcgcc tcgcggggct gctcgcctcg tcggggtttg cgttcgtcaa cgcggcccac 1200

gcccacgacg cgattcgcct ctccgacctg ctgggctttt tggcccactc gcgcgtgctg 1260

gccggcctgg ccgcccgggg agcagcgggc tgcgcggccg actcggtgtt cctgaacgtg 1320

tccgtgttgg acccggcggc ccgcctgcgg ctggaggcgc gcctcgggca tctggtggcc 1380

gcgatcctcg agcgagagca gagcctggtg gcgcacgcgc tgggctatca gctggcgttc 1440

gtgttggaca gccccgcggc ctatggcgcg gtggccccga gcgcggcccg cctgatcgac 1500

gccctgtacg ccgagtttct cggcggccgc gcgctaaccg ccccgatggt ccgccgagcg 1560

ctgttttacg ccacggccgt cctccgggcg ccgttcctgg cgggcgcgcc ctcggccgag 1620

cagcgggaac gcgcccgccg gggcctcctc ataaccacgg ccctgtgtac gtccgacgtc 1680

gccgcggcga cccacgccga tctccgggcc gcgctagcca ggaccgacca ccagaaaaac 1740

ctcttctggc tcccggacca cttttcccca tgcgcagctt ccctgcgctt cgatctcgcc 1800

gagggcgggt tcatcctgga cgcgctggcc atggccaccc gatccgacat cccggcggac 1860

gtcatggcac aacagacccg cggcgtggcc tccgttctca cgcgctgggc gcactacaac 1920

gccctgatcc gcgccttcgt cccggaggcc acccaccagt gtagcggccc gtcgcacaac 1980

gcggagcccc ggatcctcgt gcccatcacc cacaacgcca gctacgtcgt cacccacacc 2040

cccttgcccc gcgggatcgg atacaagctt acgggcgttg acgtccgccg cccgctgttt 2100

atcacctatc tcaccgccac ctgcgaaggg cacgcgcggg agattgagcc gaagcggctg 2160

gtgcgcaccg aaaaccggcg cgacctcggc ctcgtggggg ccgtgtttct gcgctacacc 2220

ccggccgggg aggtcatgtc ggtgctgctg gtggacacgg atgccaccca acagcagctg 2280

gcccaggggc cggtggcggg caccccgaac gtgttttcca gcgacgtgcc gtccgtggcc 2340

ctgttgttgt tccccaacgg aactgtgatt catctgctgg cctttgacac gctgcccatc 2400

gccaccatcg cccccgggtt tctggccgcg tccgcgctgg gggtcgttat gattaccgcg 2460

gccctggcgg gcatccttag ggtggtccga acgtgcgtcc catttttgtg gagacgcgaa 2520

taa 2523

<210> 16

<211> 681

<212> DNA

<213> herpes simplex virus type 2 (strain HG 52)

<220>

<223> coding region of HSV strain HG52 glycoprotein gL having Kozak sequence

<400> 16

ctcgctatgg ggttcgtctg tctgtttggg cttgtcgtta tgggagcctg gggggcgtgg 60

ggtgggtcac aggcaaccga atatgttctt cgtagtgtta ttgccaaaga ggtgggggac 120

atactaagag tgccttgcat gcggaccccc gcggacgatg tttcttggcg ctacgaggcc 180

ccgtccgtta ttgactatgc ccgcatagac ggaatatttc ttcgctatca ctgcccgggg 240

ttggacacgt ttttgtggga taggcacgcc cagagggcgt atctggttaa cccctttctc 300

tttgcggcgg gatttttgga ggacttgagt cactctgtgt ttccggccga cacccaggaa 360

acaacgacgc gccgggccct ttataaagag atacgcgatg cgttgggcag tcgaaaacag 420

gccgtcagcc acgcacccgt cagggccggg tgtgtaaact ttgactactc acgcactcgc 480

cgctgcgtcg ggcgacgcga tttacggcct gccaacacca cgtcaacgtg ggaaccgcct 540

gtgtcgtcgg acgatgaagc gagctcgcag tcgaagcccc tcgccaccca gccgcccgtc 600

ctcgcccttt cgaacgcccc cccacggcgg gtctccccga cgcgaggtcg gcgccggcat 660

actcgcctcc gacgcaacta g 681

<210> 17

<211> 2721

<212> DNA

<213> artificial sequence

<220>

<223> mutant glycoprotein gB of HSV2 strain HG52 having Kozak sequence

Coding sequence A784G

<400> 17

cccgccatgc gcgggggggg cttgatttgc gcgctggtcg tgggggcgct ggtggccgcg 60

gtggcgtcgg cggccccggc ggccccggcg gccccccgcg cctcgggcgg cgtggccgcg 120

accgtcgcgg cgaacggggg tcccgcctcc cggccgcccc ccgtcccgag ccccgcgacc 180

accaaggccc ggaagcggaa aaccaaaaag ccgcccaagc ggcccgaggc gaccccgccc 240

cccgacgcca acgcgaccgt cgccgccggc cacgccacgc tgcgcgcgca cctgcgggaa 300

atcaaggtcg agaacgccga tgcccagttt tacgtgtgcc cgcccccgac gggcgccacg 360

gtggtgcagt ttgagcagcc gcgccgctgc ccgacgcgcc cggaggggca gaactacacg 420

gagggcatcg cggtggtctt caaggagaac atcgccccgt acaaattcaa ggccaccatg 480

tactacaaag acgtgaccgt gtcgcaggtg tggttcggcc accgctactc ccagtttatg 540

gggatattcg aggaccgcgc ccccgttccc ttcgaggagg tgatcgacaa gattaacgcc 600

aagggggtct gccgctccac ggccaagtac gtgcggaaca acatggagac caccgcgttt 660

caccgggacg accacgagac cgacatggag ctcaagccgg cgaaggtcgc cacgcgcacg 720

agccgggggt ggcacaccac cgacctcaag tacaacccct cgcgggtgga ggcgttccat 780

cggtacggcg cgacggtcaa ctgcatcgtc gaggaggtgg acgcgcggtc ggtgtacccg 840

tacgatgagt ttgtgctggc gacgggcgac tttgtgtaca tgtccccgtt ttacggctac 900

cgggaggggt cgcacaccga gcacaccagc tacgccgccg accgcttcaa gcaggtcgac 960

ggcttctacg cgcgcgacct caccacgaag gcccgggcca cgtcgccgac gacccgcaac 1020

ttgctgacga cccccaagtt taccgtggcc tgggactggg tgccgaagcg accggcggtc 1080

tgcaccatga ccaagtggca ggaggtggac gagatgctcc gcgccgagta cggcggctcc 1140

ttccgcttct cctccgacgc catctcgacc accttcacca ccaacctgac cgagtactcg 1200

ctctcgcgcg tcgacctggg cgactgcatc ggccgggatg cccgcgaggc catcgaccgc 1260

atgtttgcgc gcaagtacaa cgccacgcac atcaaggtgg gccagccgca gtactacctg 1320

gccacggggg gcttcctcat cgcgtaccag cccctcctca gcaacacgct cgccgagctg 1380

tacgtgcggg agtacatgcg ggagcaggac cgcaagcccc ggaatgccac gcccgcgcca 1440

ctgcgggagg cgcccagcgc caacgcgtcc gtggagcgca tcaagaccac ctcctcgatc 1500

gagttcgccc ggctgcagtt tacgtataac cacatacagc gccacgtgaa cgacatgctg 1560

gggcgcatcg ccgtcgcgtg gtgcgagctg cagaaccacg agctgactct ctggaacgag 1620

gcccgcaagc tcaaccccaa cgccatcgcc tccgccaccg tcggccggcg ggtgagcgcg 1680

cgcatgctcg gagacgtcat ggccgtctcc acgtgcgtgc ccgtcgcccc ggacaacgtg 1740

atcgtgcaga actcgatgcg cgtcagctcg cggccgggga cgtgctacag ccgccccctg 1800

gtcagctttc ggtacgaaga ccagggcccg ctgatcgagg ggcagctggg cgagaacaac 1860

gagctgcgcc tcacccgcga cgcgctcgag ccgtgcaccg tgggccaccg gcgctacttc 1920

atcttcggcg ggggctacgt gtacttcgag gagtacgcgt actctcacca gctgagtcgc 1980

gccgacgtca ccaccgtcag caccttcatc gacctgaaca tcaccatgct ggaggaccac 2040

gagtttgtgc ccctggaggt ctacacgcgc cacgagatca aggacagcgg cctgctggac 2100

tacacggagg tccagcgccg caaccagctg cacgacctgc gctttgccga catcgacacg 2160

gtcatccgcg ccgacgccaa cgccgccatg ttcgcggggc tgtgcgcgtt cttcgagggg 2220

atgggggact tggggcgcgc ggtcggcaag gtagtcatgg gagtagtggg gggcgtggtg 2280

tcggccgtct cgggcgtgtc ctcctttatg tccaacccct tcggggcgct tgccgtgggg 2340

ctgctggtcc tggccggcct ggtcgcggcc ttcttcgcct tccgctacgt cctgcaactg 2400

caacgcaatc ccatgaaggc cctgtatccg ctcaccacca aggaactcaa gacttccgac 2460

cccgggggcg tgggcgggga gggggaggaa ggcgcggagg ggggcgggtt tgacgaggcc 2520

aagttggccg aggcccgaga aatgatccga tatatggctt tggtgtcggc catggagcgc 2580

acggaacaca aggccagaaa gaagggcacg agcgccctgc tcagctccaa ggtcaccaac 2640

atggttctgc gcaagcgcaa caaagccagg tactctccgc tccacaacga ggacgaggcc 2700

ggagacgaag acgagctcta a 2721

<210> 18

<211> 1188

<212> DNA

<213> herpes simplex virus type 2 (strain HG 52)

<220>

<223> coding sequence for HG52 glycoprotein gD of HSV2 strain having self-Kozak sequence

<400> 18

cacggcatgg ggcgtttgac ctccggcgtc gggacggcgg ccctgctagt tgtcgcggtg 60

ggactccgcg tcgtctgcgc caaatacgcc ttagcagacc cctcgcttaa gatggccgat 120

cccaatcgat ttcgcgggaa gaaccttccg gttttggacc agctgaccga cccccccggg 180

gtgaagcgtg tttaccacat tcagccgagc ctggaggacc cgttccagcc ccccagcatc 240

ccgatcactg tgtactacgc agtgctggaa cgtgcctgcc gcagcgtgct cctacatgcc 300

ccatcggagg ccccccagat cgtgcgcggg gcttcggacg aggcccgaaa gcacacgtac 360

aacctgacca tcgcctggta tcgcatggga gacaattgcg ctatccccat cacggttatg 420

gaatacaccg agtgccccta caacaagtcg ttgggggtct gccccatccg aacgcagccc 480

cgctggagct actatgacag ctttagcgcc gtcagcgagg ataacctggg attcctgatg 540

cacgcccccg ccttcgagac cgcgggtacg tacctgcggc tagtgaagat aaacgactgg 600

acggagatca cacaatttat cctggagcac cgggcccgcg cctcctgcaa gtacgctctc 660

cccctgcgca tccccccggc agcgtgcctc acctcgaagg cctaccaaca gggcgtgacg 720

gtcgacagca tcgggatgct accccgcttt atccccgaaa accagcgcac cgtcgcccta 780

tacagcttaa aaatcgccgg gtggcacggc cccaagcccc cgtacaccag caccctgctg 840

ccgccggagc tgtccgacac caccaacgcc acgcaacccg aactcgttcc ggaagacccc 900

gaggactcgg ccctcttaga ggatcccgcc gggacggtgt cttcgcagat ccccccaaac 960

tggcacatcc cgtcgatcca ggacgtcgcg ccgcaccacg cccccgccgc ccccagcaac 1020

ccgggcctga tcatcggcgc gctggccggc agtaccctgg cggtgctggt catcggcggt 1080

attgcgtttt gggtacgccg ccgcgctcag atggccccca agcgcctacg tctcccccac 1140

atccgggatg acgacgcgcc cccctcgcac cagccattgt tttactag 1188

<210> 19

<211> 2724

<212> DNA

<213> human gamma herpes virus 4

<220>

<223> NC_007505.1:c79865-77142 human gamma herpes virus 4tp1 genome gp350

BLLF1

<400> 19

atggaggcag ccttgcttgt gtgtcagtac accatccaga gcctgatcca tctcacgggt 60

gaagatcctg gttttttcaa tgttgagatt ccggaattcc cattttaccc cacatgcaat 120

gtttgcacgg cagatgtcaa tgtaactatc aatttcgatg tcgggggcaa aaagcatcaa 180

cttgatcttg actttggcca gctgacaccc catacgaagg ctgtctacca acctcgaggt 240

gcatttggtg gctcagaaaa tgccaccaat ctctttctac tggagctcct tggtgcagga 300

gaattggctc taactatgcg gtctaagaag cttccaatta acgtcaccac cggagaggag 360

caacaagtaa gcctggaatc tgtagatgtc tactttcaag atgtgtttgg aaccatgtgg 420

tgccaccatg cagaaatgca aaaccccgtg tacctgatac cagaaacagt gccatacata 480

aagtgggata actgtaattc taccaatata acggcagtag tgagggcaca ggggctggat 540

gtcacgctac ccttaagttt gccaacgtca gctcaagact cgaatttcag cgtaaaaaca 600

gaaatgctcg gtaatgagat agatattgag tgtattatgg aggatggcga aatttcacaa 660

gttctgcccg gagacaacaa atttaacatc acctgcagtg gatacgagag ccatgttccc 720

agcggcggaa ttctcacatc aacgagtccc gtggccaccc caatacctgg tacagggtat 780

gcatacagcc tgcgtctgac accacgtcca gtgtcacgat ttcttggcaa taacagtatc 840

ctgtacgtgt tttactctgg gaatggaccg aaggcgagcg ggggagatta ctgcattcag 900

tccaacattg tgttctctga tgagattcca gcttcacagg acatgccgac aaacaccaca 960

gacatcacat atgtgggtga caatgctacc tattcagtgc caatggtcac ttctgaggac 1020

gcaaactcgc caaatgttac agtgactgcc ttttgggcct ggccaaacaa cactgaaact 1080

gactttaagt gcaaatggac tctcacctcg gggacacctt cgggttgtga aaatatttct 1140

ggtgcatttg cgagcaatcg gacatttgac attactgtct cgggtcttgg cacggccccc 1200

aagacactca ttatcacacg aacggctacc aatgccacca caacaaccca caaggttata 1260

ttctccaagg cacccgagag caccaccacc tcccctacct tgaatacaac tggatttgct 1320

gatcccaata caacgacagg tctacccagc tctactcacg tgcctaccaa cctcaccgca 1380

cctgcaagca caggccccac tgtatccacc gcggatgtca ccagcccaac accagccggc 1440

acaacgtcag gcgcatcacc ggtgacacca agtccatctc catgggacaa cggcacagaa 1500

agtaaggccc ccgacatgac cagctccacc tcaccagtga ctaccccaac cccaaatgcc 1560

accagcccca ccccagcagt gactacccca accccaaatg ccaccagccc caccccagca 1620

gtgactaccc caaccccaaa tgccaccagc cccaccttgg gaaaaacaag tcctacctca 1680

gcagtgacta ccccaacccc aaatgccacc agccccacct tgggaaaaac aagccccacc 1740

tcagcagtga ctaccccaac cccaaatgcc accagcccca ccttgggaaa aacaagcccc 1800

acctcagcag tgactacccc aaccccaaat gccaccggcc ctactgtggg agaaacaagt 1860

ccacaggcaa atgccaccaa ccacacctta ggaggaacaa gtcccacccc agtagttacc 1920

agccaaccaa aaaatgcaac cagtgctgtt accacaggcc aacataacat aacttcaagt 1980

tcaacctctt ccatgtcact gagacccagt tcaaacccag agacactcag cccctccacc 2040

agtgacaatt caacgtcaca tatgccttta ctaacctccg ctcacccaac aggtggtgaa 2100

aatataacac aggtgacacc agcctctatc agcacacatc atgtgtccac cagttcgcca 2160

gcaccccgcc caggcaccac cagccaagcg tcaggccctg gaaacagttc cacatccaca 2220

aaaccggggg aggttaatgt caccaaaggc acgccccccc aaaatgcaac gtcgccccag 2280

gcccccagtg gccaaaagac ggcggttccc acggtcacct caacaggtgg aaaggccaat 2340

tctaccaccg gtggaaagca caccacagga catggagccc ggacaagtac agagcccacc 2400

acagattacg gcggtgattc aactacgcca agaccgagat acaatgcgac cacctatcta 2460

cctcccagca cttctagcaa actgcggccc cgctggactt ttacgagccc accggttacc 2520

acagcccaag ccaccgtgcc agtcccgcca acgtcccagc ccagattctc aaacctctcc 2580

atgctagtac tgcagtgggc ctctctggct gtgctgaccc ttctgctgct gctggtcatg 2640

gcggactgcg cctttaggcg taacttgtct acatcccata cctacaccac cccaccatat 2700

gatgacgccg agacctatgt ataa 2724

<210> 20

<211> 672

<212> DNA

<213> human gamma herpes virus 4

<220>

<223> NC_007505.1:c89828-89157 human gamma herpes virus 4tp1 genome, gp42

BZLF2

<400> 20

atggtttcat ttaagcaggt gagggtgcca ttgtttaccg ccatcgcact tgttattgtt 60

ctactcctgg catacttttt gccacccagg gtaagaggag gagggcgggt ggcagccgcg 120

gccatcacct gggtacccaa accaaatgta gaggtctggc cggtggatcc tccaccgccg 180

gttaacttta acaagacggc cgagcaggag tatggggaca aagaggtaaa actgccacat 240

tggacaccca ccctgcacac atttcaggta ccccaaaact ataccaaagc taactgtaca 300

tactgcaaca ccagagaata cacattttca tataaaggat gctgttttta tttcaccaaa 360

aagaagcaca cctggaatgg gtgtttccaa gcctgtgcag agctatatcc atgcacttat 420

ttttatgggc caacgcccga tattctacct gtggtaacta gaaatctgaa tgccattgag 480

tccctttggg tcggggtgta cagggtggga gaagggaact ggacatcatt agatgggggg 540

acttttaagg tttatcaaat ttttggctct cattgtacat atgtcagcaa atttagtaca 600

gttccagtct cacaccatga gtgttcattc cttaaaccat gtttatgtgt cagtcaaaga 660

tcaaatagct aa 672

<210> 21

<211> 2574

<212> DNA

<213> human gamma herpes virus 4

<220>

<223> NC_007505.1: c158864-156291 human gamma herpes virus 4tp1 genome gB

BALF4

<400> 21

atgactcggc gtagggtgct aagcgtggtc gtgctgctag ccgccctggc gtgccgtctc 60

ggtgcgcaga ccccagagca gcccgcaccc cccgccacca cggtgcagcc taccgccacg 120

cgtcagcaaa ccagctttcc tttccgagtc tgcgagctct ccagccacgg cgacctgttc 180

cgcttctcct cggacatcca gtgtccctcg tttggcacgc gggagaatca cacggagggc 240

ctgttgatgg tgtttaaaga caacattatt ccctactcgt ttaaggtccg ctcctacacc 300

aagatagtga ccaacattct catctacaat ggctggtacg cggactccgt gaccaaccgg 360

cacgaggaga agttctccgt tgacagctac gaaactgacc agatggatac catctaccag 420

tgctacaacg cggtcaagat gacaaaagat gggctgacgc gcgtgtatgt agaccgcgac 480

ggagttaaca tcaccgtcaa cctaaagccc accgggggcc tggccaacgg ggtgcgccgc 540

tacgccagcc agacggagct ctatgacgcc cccgggtggt tgatatggac ttacagaaca 600

agaactaccg tcaactgcct gataactgac atgatggcca agtccaacag ccccttcgac 660

ttctttgtga ccaccaccgg gcagactgtg gaaatgtccc ctttctatga cgggaaaaat 720

aaggaaacct tccatgagcg ggcagactcc ttccacgtga gaactaacta caagatagtg 780

gactacgaca accgagggac gaacccgcaa ggcgaacgcc gagccttcct ggacaagggc 840

acttacacgc tatcttggaa gctcgagaac aggacagcct actgcccgct tcaacactgg 900

caaacctttg actcgaccat cgccacagaa acagggaagt caatacattt tgtgactgac 960

gagggcacct ctagcttcgt gaccaacaca accgtgggca tagagctccc ggacgccttc 1020

aagtgcatcg aagagcaggt gaacaagacc atgcatgaga agtacgaggc cgtccaggat 1080

cgttacacga agggccagga agccattaca tattttataa cgagcggagg attgttatta 1140

gcttggctac ctctgacccc gcgctcgttg gccaccgtca agaacctgac ggagcttacc 1200

actccgactt cctcaccccc cagcagtcca tcgcccccag ccccatccgc ggcccgcggg 1260

agcacccccg ccgccgttct gaggcgtcgg aggcgggatg cggggaacgc caccacaccg 1320

gtgcccccca cggcccccgg gaagtccctg ggcaccctca acaatcccgc caccgtccag 1380

atccaatttg cctacgactc cctgcgccgc cagatcaacc gcatgctggg agaccttgcg 1440

cgggcctggt gcctggagca gaagaggcag aacatggtgc tgagagaact aaccaagatt 1500

aatccaacca ccgtcatgtc cagcatctac ggtaaggcgg tggcggccaa gcgcctgggg 1560

gatgtcatct cagtctccca gtgcgtgccc gttaaccagg ccaccgtcac cctgcgcaag 1620

agcatgaggg tccctggctc cgagaccatg tgctactcgc gccccctggt gtccttcagc 1680

tttatcaacg acaccaagac ctacgaggga cagctgggca ccgacaacga gatcttcctc 1740

acaaaaaaga tgacggaggt gtgccaggcg accagccagt actacttcca gtccggcaac 1800

gagatccacg tctacaacga ctaccaccac tttaaaacca tcgagctgga cggcattgcc 1860

accctgcaga ccttcatctc actaaacacc tccctcatcg agaacattga ctttgcctcc 1920

ctggagctgt actcacggga cgaacagcgt gcctccaacg tctttgacct ggagggcatc 1980

ttccgggagt acaacttcca ggcgcaaaac atcgccggcc tgcggaagga tttggacaat 2040

gcagtgtcaa acggaagaaa tcaattcgtg gacggcctgg gggaacttat ggacagtctg 2100

ggtagcgtgg gtcagtccat caccaaccta gtcagcacgg tggggggttt gtttagcagc 2160

ctggtctctg gtttcatctc cttcttcaaa aaccccttcg gcggcatgct cattctggtc 2220

ctggtggcgg gggtggtgat cctggttatt tccctcacga ggcgcacgcg ccagatgtcg 2280

cagcagccgg tgcagatgct ctaccccggg atcgacgagc tcgctcagca acatgcctct 2340

ggtgagggtc caggcattaa tcccattagt aagacagaat tacaagccat catgttagcg 2400

ctgcatgagc aaaaccagga gcaaaagaga gcagctcaga gggcggccgg accctcagtg 2460

gccagcagag cattgcaggc agccagggac cgttttccag gcctacgcag aagacgctat 2520

cacgatccag agaccgccgc cgcactgctt ggggaggcag agactgagtt ttaa 2574

<210> 22

<211> 2121

<212> DNA

<213> human gamma herpes virus 4

<220>

<223> NC_007405.1:c130747-128627 human gamma herpes virus 4tp1 genome gH

BXLF2

<400> 22

atgcagttgc tctgtgtttt ttgcctggtg ttgctatggg aggtgggggc tgccagcctc 60

agcgaggtta agctgcacct ggacatagag gggcatgctt cgcattacac catcccatgg 120

accgaactga tggcaaaggt cccaggcctt agcccagagg cgctgtggag agaggcaaat 180

gtcaccgaag atttggcgtc tatgcttaac cgctacaagt taatttacaa gacgtctggt 240

acccttggta ttgcgctggc cgagcctgtc gatatccctg ctgtctctga aggatccatg 300

caagtggatg catctaaggt ccatcccgga gtcattagcg gcctgaattc ccctgcctgc 360

atgcttagtg ccccccttga gaagcagctc ttctactata ttggcaccat gctgcccaac 420

acgcggccac acagctatgt cttttatcag ctgcgctgtc acttgtctta tgtggccctg 480

tccatcaacg gggacaagtt tcagtacacg ggggccatga cttctaaatt tctgatgggc 540

acctacaagc gagtgaccga gaagggagat gagcatgtgt tgagcctggt ctttggcaag 600

acgaaggacc tgccggatct gagggggcct tttagttacc catccttaac cagtgcccaa 660

agcggggact attccctggt gattgttaca acctttgtgc attatgccaa ctttcacaac 720

tactttgtac ccaacctgaa ggatatgttt tcccgagccg tcaccatgac agccgccagc 780

tacgctcgct acgttctcca gaaactggtc ctgctggaga tgaagggagg ctgccgggag 840

ccggaactgg acacggaaac gctgactacc atgtttgagg tttctgtggc cttctttaag 900

gtgggtcatg ctgtgggtga gactggcaat ggctgcgtgg acctccgctg gttggccaag 960

agcttctttg agctgactgt cctgaaagac atcatcggca tatgttatgg ggccactgtc 1020

aagggcatgc aatcctacgg gctggagcgc ttggccgcca tgctgatggc cacggtcaag 1080

atggaggagc tgggtcacct gactactgag aaacaggagt acgcgctgag gttagccacc 1140

gtcggctacc ccaaggccgg ggtttacagt ggcctcattg gaggcgccac atctgtgctt 1200

ctctcggcct acaaccgcca cccccttttc cagcccctgc ataccgtgat gagagagacc 1260

ctgtttatcg gcagccacgt ggtgctacgc gagttgcggc tgaacgtgac tacccagggg 1320

cccaaccttg ccctatacca actgctgtcc accgccctgt gctcggccct agagattggg 1380

gaggttttgc gggggctagc cctggggaca gagagcgggc tcttctcacc gtgctacctc 1440

agcctacgat ttgacctcac acgagacaag ctgctgagca tggcccccca ggaggcaacg 1500

ctggaccagg cggccgtttc aaatgctgtg gatgggtttc ttgggcggct ctctttggag 1560

cgagaagaca gggatgcgtg gcatctcccc gcctacaaat gcgtggacag gctcgacaaa 1620

gttctgatga ttatcccgct catcaatgtg acattcataa tctctagtga ccgtgaggtc 1680

cgaggctcgg cgctatacga ggccagcacc acctatctca gcagctctct ctttctctcc 1740

cccgttataa tgaataaatg ttcgcagggt gctgtggctg gggagccccg ccagattcca 1800

aagatccaga attttaccag gacgcagaaa tcctgcattt tttgtggctt tgccctgctc 1860

agttatgatg aaaaggaagg cctggaaact acaacctaca tcacctccca ggaagtccaa 1920

aactccatct tgagctccaa ctactttgat tttgacaacc tccacgttca ctatctgctg 1980

ctgaccacca acgggactgt catggaaatt gcgggcctgt atgaagaaag agcacacgtt 2040

gttttggcaa taatcctgta ctttattgct tttgctctgg gtatctttct ggttcacaag 2100

attgttatgt ttttccttta g 2121

<210> 23

<211> 672

<212> DNA

<213> human gamma herpes virus 4

<220>

<223> NC_007405.1:c89828-89157 human gamma herpes virus 4tp1 genome, gL

BZLF2

<400> 23

atggtttcat ttaagcaggt gagggtgcca ttgtttaccg ccatcgcact tgttattgtt 60

ctactcctgg catacttttt gccacccagg gtaagaggag gagggcgggt ggcagccgcg 120

gccatcacct gggtacccaa accaaatgta gaggtctggc cggtggatcc tccaccgccg 180

gttaacttta acaagacggc cgagcaggag tatggggaca aagaggtaaa actgccacat 240

tggacaccca ccctgcacac atttcaggta ccccaaaact ataccaaagc taactgtaca 300

tactgcaaca ccagagaata cacattttca tataaaggat gctgttttta tttcaccaaa 360

aagaagcaca cctggaatgg gtgtttccaa gcctgtgcag agctatatcc atgcacttat 420

ttttatgggc caacgcccga tattctacct gtggtaacta gaaatctgaa tgccattgag 480

tccctttggg tcggggtgta cagggtggga gaagggaact ggacatcatt agatgggggg 540

acttttaagg tttatcaaat ttttggctct cattgtacat atgtcagcaa atttagtaca 600

gttccagtct cacaccatga gtgttcattc cttaaaccat gtttatgtgt cagtcaaaga 660

tcaaatagct aa 672

<210> 24

<211> 2661

<212> DNA

<213> human herpesvirus 4

<220>

<223> NC_009334.1: c79936-77276 human herpesvirus 4tp2 genome, gp350,

BLLF1

<400> 24

atggaggcag ccttgcttgt gtgtcagtac accatccaga gccttatcca actcacgcgt 60

gatgatcctg gttttttcaa tgttgagatt ctggaattcc cattttaccc agcgtgcaat 120

gtttgcacgg cagatgtcaa tgcaactatc aatttcgatg tcgggggcaa aaagcataaa 180

cttaatcttg actttggcct gctgacaccc catacaaagg ctgtctacca acctcgaggt 240

gcatttggtg gctcagaaaa tgccaccaat ctctttctac tggagctcct tggtgcagga 300

gaattggctc taactatgcg gtctaagaag cttccaatta acatcaccac cggagaggag 360

caacaagtaa gcctggaatc tgtagatgtc tactttcaag atgtgtttgg caccatgtgg 420

tgccaccatg cagaaatgca aaacccagta tacctaatac cagaaacagt gccatacata 480

aagtgggata actgtaattc taccaatata acggcagtag taagggcaca ggggctggat 540

gtcacgctac ccttaagttt gccaacatca gctcaagact cgaatttcag cgtaaaaaca 600

gaaatgctcg gtaatgagat agatattgag tgtattatgg aggatggcga aatttcacaa 660

gttctgcccg gagacaacaa atttaacatc acctgcagtg gatacgagag ccatgttccc 720

agcggcggaa ttctcacatc aacgagtccc gtggccaccc caatacctgg tacagggtat 780

gcatacagcc tgcgtctgac accacgtcca gtgtcacgat ttcttggcaa taacagtata 840

ctgtacgtgt tttactctgg gaatggaccg aaggcgagcg ggggagatta ctgcattcag 900

tccaacattg tgttctctga tgagattcca gcttcacagg acatgccgac aaacaccaca 960

gacatcacat atgtgggtga caatgctacc tattcagtgc caatggtcac ttctgaggac 1020

gcaaactcgc caaatgttac agtgactgcc ttttgggcct ggccaaacaa cactgaaact 1080

gactttaagt gcaaatggac tctcacctcg gggacacctt cgggttgtga aaatatttct 1140

ggtgcatttg cgagcaatcg gacatttgac attactgtct cgggtcttgg cacggccccc 1200

aagacactca ttatcacacg aacggctacc aatgccacca caacaaccca caaggttata 1260

ttctccaagg cacccgagag caccaccacc tcccctacct tgaatacaac tggatttgct 1320

gctcccaata caacgacagg tctacccagc tctactcacg tgcctaccaa cctcaccgca 1380

cctgcaagca caggccccac tgtatccacc gcggatgtca ccagcccaac accagccggc 1440

acaacgtcag gcgcatcacc ggtgacacca agtccatctc cacgggacaa cggcacagaa 1500

agtaaggccc ccgacatgac cagccccacc tcagcagtga ctaccccaac cccaaatgcc 1560

accagcccca ccccagcagt gactacccca accccaaatg ccaccagccc caccttggga 1620

aaaacaagtc ccacctcagc agtgactacc ccaaccccaa atgccaccag ccccacccca 1680

gcagtgacta ccccaacccc aaatgccacc atccccacct tgggaaaaac aagtcccacc 1740

tcagcagtga ctaccccaac cccaaatgcc accagcccta ccgtgggaga aacaagtcca 1800

caggcaaata ccaccaacca cacattagga ggaacaagtt ccaccccagt agttaccagc 1860

ccaccaaaaa atgcaaccag tgctgttacc acaggccaac ataacataac ttcaagttca 1920

acctcttcca tgtcactgag acccagttca atctcagaga cactcagccc ctccaccagt 1980

gacaattcaa cgtcacatat gcctttacta acctccgctc acccaacagg tggtgaaaat 2040

ataacacagg tgacaccagc ctctaccagc acacatcatg tgtccaccag ttcgccagcg 2100

ccccgcccag gcaccaccag ccaagcgtca ggccctggaa acagttccac atccacaaaa 2160

ccgggggagg ttaatgtcac caaaggcacg ccccccaaaa atgcaacgtc gccccaggcc 2220

cccagtggcc aaaagacggc ggttcccacg gtcacctcaa caggtggaaa ggccaattct 2280

accaccggtg gaaagcacac cacaggacat ggagcccgga caagtacaga gcccaccaca 2340

gattacggcg gtgattcaac tacgccaaga acgagataca atgcgaccac ctatctacct 2400

cccagcactt ctagcaaact gcggccccgc tggactttta cgagcccacc ggttaccaca 2460

gcccaagcca ccgtgcctgt cccgccaacg tcccagccca gattctcaaa cctctccatg 2520

ctagtactgc agtgggcctc tctggctgtg ctgacccttc tgctgctgct ggtcatggcg 2580

gactgcgcct tcaggcgtaa cttgtcgaca tcccatacct acaccacccc accatatgat 2640

gacgccgaga cctatgtata a 2661

<210> 25

<211> 672

<212> DNA

<213> human herpesvirus 4

<220>

<223> NC_009334.1:c90630-89959 human herpesvirus 4tp2 genome, gp42

<400> 25

atggtttcgt ttaagcaggt gagggtgcca ttgtttaccg ccatcgcact tgttattgtt 60

ctactcctgg catacttttt gccacccagg gtaagaggag gagggcgggt gtcggcagcg 120

gccatcacct gggtacccaa accaaatgta gaggtctggc cggtggatcc tccaccgccg 180

gttaacttta acaagacggc cgagcaggag tatggggaca aagagataaa actgccacat 240

tggacaccca ccctgcacac gtttcaggta cccaaaaact ataccaaagc taactgtaca 300

tactgcaaca caagagaata cacattttca tataaagaac gctgttttta tttcaccaaa 360

aagaagcaca cctggaatgg gtgtttccaa gcctgtgcag agctatatcc atgcacttat 420

ttttatgggc caacgcccga tattctacct gtggtaacta gaaatctgaa tgccattgag 480

tccctttggg tcggggtgta cagggtggga gaagggaact ggacatcatt agatgggggg 540

acttttaagg tttatcaaat ttttggctct cattgtacat atgtcagcaa atttagtaca 600

gttccagtct cacaccatga gtgttcattc cttaaaccat gtttatgtgt cagtcaaaga 660

tcaaatagct aa 672

<210> 26

<211> 2574

<212> DNA

<213> human herpesvirus 4

<220>

<223> NC_009334.1:c160348-157775 human herpesvirus 4tp2 genome,

glycoprotein B BALF4

<400> 26

atgactcggc gtagggtgct aagcgtggtc gtgctgctag ccgccctggc gtgccgcctc 60

ggtgcgcaga ccccagagca gcccgcaccc cccgccacca cggtgcagcc taccgccacg 120

cgtcagcaaa ccagctttcc tttccgagtc tgcgagctct ccagccacgg cgacctgttc 180

cgcttctcct cggacatcca gtgtccctcg tttggcacgc gggagaatca cacggagggc 240

ctgttgatgg tgtttaaaga caacattatt ccctactcgt ttaaggtccg ctcctacacc 300

aagatagtga ccaacattct catctacaat ggctggtacg cggactccgt gaccaaccgg 360

cacgaggaga agttctccgt tgacagctac gaaactgacc agatggatac catctaccag 420

tgctacaacg cggtcaagat gacaaaagat gggctgacgc gcgtgtatgt agaccgcgac 480

ggagttaaca tcaccgtcaa cctaaagccc accgggggcc tggccaacgg ggtgcgccgc 540

tacgccagcc agacggagct ctatgacgcc cccgggtggt tgatatggac ttacagaaca 600

agaactaccg tcaactgcct gataactgac atgatggcca agtccaacag ccccttcgac 660

ttctttgtga ccaccaccgg gcagactgtg gaaatgtccc ctttctatga cgggaaaaat 720

aaggaaacct tccatgagcg ggcagactcc ttccacgtga gaactaacta caagatagtg 780

gactacgaca accgagggac gaacccgcaa ggcgaacgcc gagccttcct ggacaagggc 840

acttacaccc tatcttggaa gctcgagaac aggacagcct actgcccgct tcaacactgg 900

caaacctttg actcgaccat cgccacagaa acagggaagt caatacattt tgtgactgac 960

gagggcacct ctagcttcgt gaccaacaca accgtgggca tagagctccc ggacgccttc 1020

aagtgcatcg aagagcaggt gaacaagacc atgcatgaga agtacgaggc cgtccaggat 1080

cgttacacga agggccagga agccattaca tattttataa cgagcggagg attgttatta 1140

gcttggctac ctctgacccc gcgctcgttg gccaccgtca agaacctgac ggagcttacc 1200

actccgactt cctcaccccc cagcagtcca tcgccccccg ccccacccgc ggcccgcggg 1260

agcacctccg ccgccgttct gaggcgccgg aggcgggatg cggggaatgc caccacaccg 1320

gtgccccccg cggcccccgg gaagtccctg ggcaccctca acaatcccgc caccgtccag 1380

atccaatttg cctacgattc cctgcgccgc cagatcaacc gcatgctggg agacctcgcg 1440

cgggcctggt gcctggagca gaagaggcag aacatggtgc tgagagaact aaccaagatt 1500

aatcccacca ccgtcatgtc cagcatctac ggtaaggcgg tggcggccaa gcgcctgggg 1560

gatgtcatct cagtctccca gtgcgtgccc gttaaccagg ccaccgtcac cctgcgcaag 1620

agcatgaggg tccctggctc cgagaccatg tgctactcgc gccccctggt gtccttcagc 1680

tttatcaacg acaccaagac ctacgaggga cagctgggca ccgacaacga gatcttcctc 1740

acaaaaaaga tgacggaggt gtgccaggcg accagccagt actacttcca gtccggcaac 1800

gagatccacg tctacaacga ctaccaccac tttaaaacca tcgagctgga cggcattgcc 1860

accctgcaga ccttcatctc actaaacacc tccctcatcg agaacattga ctttgcctcc 1920

ctggagctgt actcacggga cgaacagcgt gcctccaacg tctttgacct ggagggcatc 1980

ttccgggagt acaacttcca ggcgcaaaac atcgccggcc tgcggaagga tttggacaat 2040

gcagtgtcaa acggaagaaa tcaattcgtg gacggcctgg gggaacttat ggacagtctg 2100

ggtagcgtgg gtcagtccat caccaaccta gtcagcacgg tggggggttt gtttagcagc 2160

ctggtctctg gtttcatctc cttcttcaaa aaccccttcg gcggcatgct cattctggtc 2220

ctggtggcgg gggtggtgat cctggttatt tccctcacga ggcgcacgcg ccagatgtcg 2280

cagcagccgg tgcagatgct ctaccccggg atcgacgagc tcgctcagca acatgcctct 2340

ggtgagggtc caggcattaa tcccattagt aagacagaat tacaagccat catgttagcg 2400

ctgcatgagc aaaaccagga gcaaaagaga gcagctcaga gggcggccgg accctcagtg 2460

gccagcagag cattgcaggc agccagggac cgttttccag gcctacgcag aagacgctat 2520

cacgatccag agaccgccgc cgcactgctt ggggaggcag agactgagtt ttaa 2574

<210> 27

<211> 2121

<212> DNA

<213> human herpesvirus 4

<220>

<223> NC_009334.1:c131574-129454 human herpesvirus 4tp2 genome,

glycoprotein H BXLF2 gp85

<400> 27

atgcagttgc tctgtgtttt ttgcctggtg ttgctatggg aggtgggggc tgccagtctc 60

agcgaggtta agctgcacct ggacatagag gggcatgctt cgcattacac catcccatgg 120

accgaactga tggcaaaggt cccaggcctt agcccagagg cgctgtggag agaggcaaat 180

gtcaccgaag atttggcgtc tatgcttaac cgctacaagt taatttacaa gacgtctggt 240

acccttggta ttgcgctggc cgagcctgtc gatatccctg ctgtctctga aggatccatg 300

caagtggatg catctaaggt ccatcccgga gtcattagcg gcctgaattc ccctgcctgc 360

atgcttagtg ccccccttga gaagcagctc ttctactata ttggcaccat gctgcccaac 420

acgcggccac acagctatgt cttttatcag ctgcgctgtc acttgtctta tgtggccctg 480

tccatcaacg gggacaagtt tcagtacacg ggggccatga cttctaaatt tctgatgggc 540

acctacaagc gagtgaccga gaagggagat gagcatgtgt tgagcctgat ctttggcaag 600

acgaaggacc tgccggatct gagggggcct tttagttacc catccttaac cagtgcccaa 660

agcggggact attccctggt gattgttaca acctttgtgc attatgccaa ctttcacaac 720

tactttgtac ccaacctgaa ggatatgttt tcccgagccg tcaccatgac agccgccagc 780

tacgctcgct acgttctcca gaaactggtc ctgctggaga tgaagggagg ctgccgggag 840

ccagaactgg acacggaaac gctgactacc atgtttgagg tttctgtggc cttctttaag 900

gtgggtcatg ccgtgggtga gactggcaat ggctgcgtgg acctccgctg gttggccaag 960

agcttctttg agctgactgt cctgaaagac atcatcggca tatgttatgg ggccactgtc 1020

aagggcatgc aatcctacgg gctggagcgc ttggccgccg tgctgatggc cacggtcaag 1080

atggaggagc ttggtcacct gacgactgag aaacaggagt acgcgctgag gttagccacc 1140

gtcggctacc ccaaggccgg ggtttacagt ggcctcattg gaggcgccac atctgtgctt 1200

ctctcggcct acaaccgcca cccccttttc cagcccctgc ataccgtgat gagagagacc 1260

ctgtttatcg gcagccacgt ggtgctacgc gagttgcggc tgaacgtgac tacccagggg 1320

cccaaccttg ccctatacca actgctgtcc accgccctgt gctcggccct agagattggg 1380

gaggttttgc gggggctagc cctggggacg gagagcgggc tcttctcacc gtgctacctc 1440

agcctacgat ttgacctcac acgagacaag ctgctgagca tggcccccca ggaggcaatg 1500

ctggaccagg cggccgtttc aaatgctgtg gatgggtttc ttgggcgtct ctctttggag 1560

cgagaagaca gggatgcgtg gcatctcccc gcctacaaat gcgtggacag gctcgacaaa 1620

gttctgatga ttatcccgct catcaacgtg acattcataa tctctagtga ccgtgaggtc 1680

cgaggctcgg cgctatacga ggccagcacc acctatctca gcagctctct ctttctctcc 1740

cccgttataa tgaataaatg ttcgcagggt gctgtggctg gggagccccg ccagattcca 1800

aagatccaga attttaccag gacgcagaaa tcctgcattt tttgtggctt tgccctgctc 1860

agttatgatg aaaaggaagg cctggaaact acaacctaca tcacctccca ggaagtccaa 1920

aactccatct tgagctccaa ctactttgat tttgacaacc tccacgttca ctatctgctg 1980

ctgaccacca acgggactgt catggaaatt gcgggcctgt atgaagaaag agcacacgtt 2040

gttttggcaa taatcctgta ctttattgct tttgctctgg gtatctttct ggttcacaag 2100

attgttatgt ttttccttta g 2121

<210> 28

<211> 414

<212> DNA

<213> human herpesvirus 4

<220>

<223> NC_009334.1:98500-98913 human herpesvirus 4tp2 genome,

glycoprotein gL BKRF2

<400> 28

atgcgtactg ttggtgtatt tctggccacc tgtcttgtca ccattttcgt cctcccaaca 60

tggggcaatt gggcataccc atgttgtcac gtcactcagc tccgcgctca acaccttctc 120

gcgttggaaa acattagcga catttacctg gtgagcaatc agacatgcga cggctttagc 180

ctggcctcct taaattcacc taagaatggg agcaaccagc tggtcatcag ccgctgcgca 240

aacggactca acgtggtctc cttctttatc tccatcctga agcgaagcag ctccgccctc 300

acgggccatc tccgtgagtt gttaaccacc ctggagactc tttacggttc attctcagtg 360

gaagacctgt ttggtgccaa cttaaacaga tacgcatggc atcgcggggg ctag 414

<210> 29

<211> 2724

<212> DNA

<213> human herpesvirus 5 Merlin

<220>

<223> NC_006273.2:c84789-82066 human herpesvirus 5 Merlin genome

UL55 gB

<400> 29

atggaatcca ggatctggtg cctggtagtc tgcgttaact tgtgtatcgt ctgtctgggt 60

gctgcggttt cctcatcttc tactcgtgga acttctgcta ctcacagtca ccattcctct 120

catacgacgt ctgctgctca ctctcgatcc ggttcagtct ctcaacgcgt aacttcttcc 180

caaacggtca gccatggtgt taacgagacc atctacaaca ctaccctcaa gtacggagat 240

gtggtggggg tcaataccac caagtacccc tatcgcgtgt gttctatggc ccagggtacg 300

gatcttattc gctttgaacg taatatcgtc tgcacctcga tgaagcccat caatgaagac 360

ctggacgagg gcatcatggt ggtctacaaa cgcaacatcg tcgcgcacac ctttaaggta 420

cgagtctacc agaaggtttt gacgtttcgt cgtagctacg cttacatcca caccacttat 480

ctgctgggca gcaacacgga atacgtggcg cctcctatgt gggagattca tcatatcaac 540

agccacagtc agtgctacag ttcctacagc cgcgttatag caggcacggt tttcgtggct 600

tatcataggg acagctatga aaacaaaacc atgcaattaa tgcccgacga ttattccaac 660

acccacagta cccgttacgt gacggtcaag gatcaatggc acagccgcgg cagcacctgg 720

ctctatcgtg agacctgtaa tctgaattgt atggtgacca tcactactgc gcgctccaaa 780

tatccttatc attttttcgc cacttccacg ggtgacgtgg ttgacatttc tcctttctac 840

aacggaacca atcgcaatgc cagctacttt ggagaaaacg ccgacaagtt tttcattttt 900

ccgaactaca ctatcgtctc cgactttgga agaccgaatt ctgcgttaga gacccacagg 960

ttggtggctt ttcttgaacg tgcggactcg gtgatctcct gggatataca ggacgaaaag 1020

aatgtcactt gtcaactcac tttctgggaa gcctcggaac gcaccattcg ttccgaagcc 1080

gaggactcgt atcacttttc ttctgccaaa atgaccgcca ctttcttatc taagaagcaa 1140

gaggtgaaca tgtccgactc tgcgctggac tgcgtacgtg atgaggctat aaataagtta 1200

cagcagattt tcaatacttc atacaatcaa acatatgaaa aatatggaaa cgtgtccgtc 1260

tttgaaacca ctggtggttt ggtagtgttc tggcaaggta tcaagcaaaa atctctggtg 1320

gaactcgaac gtttggccaa ccgctccagt ctgaatctta ctcataatag aaccaaaaga 1380

agtacagatg gcaacaatgc aactcattta tccaacatgg aatcggtgca caatctggtc 1440

tacgcccagc tgcagttcac ctatgacacg ttgcgcggtt acatcaaccg ggcgctggcg 1500

caaatcgcag aagcctggtg tgtggatcaa cggcgcaccc tagaggtctt caaggaactc 1560

agcaagatca acccgtcagc cattctctcg gccatttaca acaaaccgat tgccgcgcgt 1620

ttcatgggtg atgtcttggg cctggccagc tgcgtgacca tcaaccaaac cagcgtcaag 1680

gtgctgcgtg atatgaacgt gaaggagtcg ccaggacgct gctactcacg acccgtggtc 1740

atctttaatt tcgccaacag ctcgtacgtg cagtacggtc aactgggcga ggacaacgaa 1800

atcctgttgg gcaaccaccg cactgaggaa tgtcagcttc ccagcctcaa gatcttcatc 1860

gccgggaact cggcctacga gtacgtggac tacctcttca aacgcatgat tgacctcagc 1920

agtatctcca ccgtcgacag catgatcgcc ctggatatcg acccgctgga aaataccgac 1980

ttcagggtac tggaacttta ctcgcagaaa gagctgcgtt ccagcaacgt ttttgacctc 2040

gaagagatca tgcgcgaatt caactcgtac aagcagcggg taaagtacgt ggaggacaag 2100

gtagtcgacc cgctaccgcc ctacctcaag ggtctggacg acctcatgag cggcctgggc 2160

gccgcgggaa aggccgttgg cgtagccatt ggggccgtgg gtggcgcggt ggcctccgtg 2220

gtcgaaggcg ttgccacctt cctcaaaaac cccttcggag cgttcaccat catcctcgtg 2280

gccatagctg tagtcattat cacttatttg atctatactc gacagcggcg tttgtgcacg 2340

cagccgctgc agaacctctt tccctatctg gtgtccgccg acgggaccac cgtgacgtcg 2400

ggcagcacca aagacacgtc gttacaggct ccgccttcct acgaggaaag tgtttataat 2460

tctggtcgca aaggaccggg accaccgtcg tctgatgcat ccacggcggc tccgccttac 2520

accaacgagc aggcttacca gatgcttctg gccctggccc gtctggacgc agagcagcga 2580

gcgcagcaga acggtacaga ttctttggac ggacggactg gcacgcagga caagggacag 2640

aagcccaacc tactagaccg actgcgacat cgcaaaaacg gctaccgaca cttgaaagac 2700

tctgacgaag aagagaacgt ctga 2724

<210> 30

<211> 2229

<212> DNA

<213> human herpesvirus 5 Merlin

<220>

<223> NC_006273.2:c111452-109224 human herpesvirus 5 Merlin strain

Genome, gH UL75

<400> 30

atgcggccag gcctcccctc ctacctcatc atcctcgccg tctgtctctt cagccaccta 60

ctttcgtcac gatatggcgc agaagccgta tccgaaccgc tggacaaagc gtttcaccta 120

ctgctcaaca cctacgggag acccatccgc ttcctgcgtg aaaataccac ccagtgtacc 180

tacaacagca gcctccgtaa cagcacggtc gtcagggaaa acgccatcag tttcaacttt 240

ttccaaagct ataatcaata ctatgtattc catatgcctc gatgtctttt tgcgggtcct 300

ctggcggagc agtttctgaa ccaggtagat ctgaccgaaa ccctggaaag ataccaacag 360

agacttaaca cttacgcgct ggtatccaaa gacctggcca gctaccgatc tttttcgcag 420

cagctaaagg cacaagacag cctaggtgaa cagcccacca ctgtgccacc gcccattgac 480

ctgtcaatac ctcacgtttg gatgccaccg caaaccactc cacacggctg gacagaatca 540

cataccacct caggactaca ccgaccacac tttaaccaga cctgtatcct ctttgatgga 600

cacgatctac tattcagcac cgtcacacct tgtttgcacc aaggctttta cctcatcgac 660

gaactacgtt acgttaaaat aacactgacc gaggacttct tcgtagttac ggtgtccata 720

gacgacgaca cacccatgct gcttatcttc ggccatcttc cacgcgtact tttcaaagcg 780

ccctatcaac gcgacaactt tatactacga caaactgaaa aacacgagct cctggtgcta 840

gttaagaaag atcaactgaa ccgtcactct tatctcaaag acccggactt tcttgacgcc 900

gcacttgact tcaactacct agacctcagc gcactactac gtaacagctt tcaccgttac 960

gccgtggatg tactcaagag cggtcgatgt cagatgctgg accgccgcac ggtagaaatg 1020

gccttcgcct acgcattagc actgttcgca gcagcccgac aagaagaggc cggcgcccaa 1080

gtctccgtcc cacgggccct agaccgccag gccgcactct tacaaataca agaatttatg 1140

atcacctgcc tctcacaaac accaccacgc accacgttgc tgctgtatcc cacggccgtg 1200

gacctggcca aacgagccct ttggacaccg aatcagatca ccgacatcac cagcctcgta 1260

cgcctggtct acatactctc taaacagaat cagcaacatc tcatccccca atgggcacta 1320

cgacagatcg ccgactttgc cctaaaacta cacaaaacgc acctggcctc ttttctttca 1380

gccttcgcac gccaagaact ctacctcatg ggcagcctcg tccactccat gctggtacat 1440

acgacggaga gacgcgaaat cttcatcgta gaaacgggcc tctgttcatt ggccgagcta 1500

tcacacttta cgcagttgtt agctcatcca caccacgaat acctcagcga cctgtacaca 1560

ccctgttcca gtagcgggcg acgcgatcac tcgctcgaac gcctcacgcg tctcttcccc 1620

gatgccaccg tccccgctac cgttcccgcc gccctctcca tcctatctac catgcaacca 1680

agcacgctgg aaaccttccc cgacctgttt tgcttgccgc tcggcgaatc cttctccgcg 1740

ctgaccgtct ccgaacacgt cagttatatc gtaacaaacc agtacctgat caaaggtatc 1800

tcctaccctg tctccaccac cgtcgtaggc cagagcctca tcatcaccca gacggacagt 1860

caaactaaat gcgaactgac gcgcaacatg cataccacac acagcatcac agtggcgctc 1920

aacatttcgc tagaaaactg cgccttttgc caaagcgccc tgctagaata cgacgacacg 1980

caaggcgtca tcaacatcat gtacatgcac gactcggacg acgtcctttt cgccctggat 2040

ccctacaacg aagtggtggt ctcatctccg cgaactcact acctcatgct tttgaaaaac 2100

ggtacggtac tagaagtaac tgacgtcgtc gtggacgcca ccgacagtcg tctcctcatg 2160

atgtccgtct acgcgctatc ggccatcatc ggcatctatc tgctctaccg catgctcaag 2220

acatgctga 2229

<210> 31

<211> 837

<212> DNA

<213> human herpesvirus 5 Merlin

<220>

<223> NC_006273.2:c165858-165022 human herpesvirus 5 Merlin strain

Genome, gL UL115

<400> 31

atgtgccgcc gcccggattg cggcttctct ttctcacctg gaccggtgat actgctgtgg 60

tgttgccttc tgctgcccat tgtttcctca gccgccgtca gcgtcgctcc taccgccgcc 120

gagaaagtcc ccgcggagtg ccccgaacta acgcgccgat gcttgttggg tgaggtgttt 180

gagggtgaca agtatgaaag ttggctgcgc ccgttggtga atgttaccgg gcgcgatggc 240

ccgctatcgc aacttatccg ttaccgtccc gttacgccgg aggccgccaa ctccgtgctg 300

ttggacgagg ctttcctgga cactctggcc ctgctgtaca acaatccgga tcaattgcgg 360

gccctgctga cgctgttgag ctcggacaca gcgccgcgct ggatgacggt gatgcgcggc 420

tacagcgagt gcggcgatgg ctcgccggcc gtgtacacgt gcgtggacga cctgtgccgc 480

ggctacgacc tcacgcgact gtcatacggg cgcagcatct tcacggaaca cgtgttaggc 540

ttcgagctgg tgccaccgtc tctctttaac gtggtggtgg ccatacgcaa cgaagccacg 600

cgtaccaacc gcgccgtgcg tctgcccgtg agcaccgctg ccgcgcccga gggcatcacg 660

ctcttttacg gcctgtacaa cgcagtgaag gaattctgcc tgcgtcacca gctggacccg 720

ccgctgctac gccacctaga taaatactac gccggactgc cgcccgagct gaagcagacg 780

cgcgtcaacc tgccggctca ctcgcgctat ggccctcaag cagtggatgc tcgctaa 837

<210> 32

<211> 1419

<212> DNA

<213> human herpesvirus 5 Merlin

<220>

<223> NC_006273.2:c108848-107430 human herpesvirus 5 Merlin

Genome, gO5 UL74

<400> 32

atggggaaaa aagagatgat aatggtgaaa ggcattccta aaattatgct cctgatctct 60

ataacgttct tgctcctttc cctcataaat tgtaatgtat tggtaaactc cagaggaaca 120

agacgttcct ggccgtatac cgtgctatct tatcgaggta aagagattct gaagaaacag 180

aaggaagata tcttaaaacg attgatgtct acatcatctg acggataccg gtttttaatg 240

taccccagtc agcaaaaatt tcatgccatc gttattagca tggataaatt tcctcaagac 300

tacattttag cgggtcccat tagaaatgat agcattaccc atatgtggtt tgacttttac 360

agtactcaac tccgaaaacc agccaagtac gtatattccg aatataatca cacggcccac 420

aaaataacgt tacgaccccc accttgcggc acagtgcctt ctatgaactg cctatccgaa 480

atgttaaatg tttccaaacg caatgatacc ggcgaaaaag gttgcggtaa tttcaccacg 540

tttaatccta tgtttttcaa cgtaccacgt tggaacacaa aactgtacat aggttccaac 600

aaagtcaacg tggatagtca gacaatctac tttttgggcc taaccgccct acttttacga 660

tacgcgcaac gtaactgcac tcgcagtttc tacctggtta acgccatgag ccgaaattta 720

ttccgcgttc ccaagtatat taacggcacc aagttgaaaa acactatgcg aaaactcaaa 780

cgtaaacaag cgcttgtcaa agaacaacca caaaaaaaga ataagaaatc tcaaagtact 840

actacgccat atctttccta tacaacgtct accgctttca acgtcaccac taacgtgact 900

tatagtgcta ccgctgctgt aacgcgggtt gccacatcta cgacaggtta tcgtcctgat 960

agtaacttta tgaaatccat tatggccacg cagttaagag atctcgcaac atgggtatat 1020

actactctgc ggtatcggaa tgaacccttt tgtaaaccag accgtaaccg taccgccgtg 1080

tcagaattta tgaaaaacac gcacgtactg attcgtaacg aaacgccgta cactatttat 1140

ggcactcttg acatgagctc cttatattac aacgaaacca tgtccgtgga aaacgaaacg 1200

gcttccgata ataacgaaac tacacctacg tcaccatcga cgaggtttca gagaacgttc 1260

atagatcccc tatgggacta tctagactcg ctgctgtttc tagataaaat ccgtaacttt 1320

agcctccagt tacccgcgta tggaaatctt accccgccgg aacaccgccg ggctgcaaat 1380

ctatccaccc tcaatagcct ttggtggtgg tcgcagtaa 1419

<210> 33

<211> 1401

<212> DNA

<213> human herpesvirus 5 Merlin

<220>

<223> NC_001347.5:c108456-107056 human herpesvirus 5 genome AD169 varUK

gO1a UL74

<400> 33

atggggagaa aagagatgat ggtgagagac gtccctaaga tggtgtttct aatatctata 60

tctttcttgc ttgtttcttt cataaactgt aaagttatgt caaaagcgct ttataatcgt 120

ccttggaggg gcttggtact gtctaagata ggcaaatata aattagatca gcttaagtta 180

gaaattttga gacaactaga aacgactatt tctacaaaat acaatgtaag taaacaaccg 240

gttaaaaatc tcactatgaa catgacagag tttccacaat actacatttt agcgggcccc 300

attcagaatt atagtataac ctatctgtgg tttgattttt atagtaccca gcttagaaaa 360

cccgcaaaat acgtttactc acagtacaat catacggcta aaacgataac attcagaccc 420

ccaccttgtg gtactgtgcc ttccatgact tgtctttccg aaatgctaaa cgtttccaaa 480

cgtaatgata ctggcgaaca aggttgcggt aatttcacca cgttcaaccc catgtttttc 540

aatgtaccgc gttggaacac caaattgtac gtgggtccga ctaaggttaa cgtagatagt 600

caaacgattt attttctagg tttaaccgcc ctgcttttac gttacgcaca acgcaactgt 660

acacacagtt tctacctggt taacgccatg agccggaatc tatttcgcgt ccccaagtat 720

attaacggca ccaagttaaa aaacactatg cgaaaactaa aacgtaaaca agcgcccgtt 780

aaggaacaat tcgaaaaaaa agctaagaaa actcagagta ctactacgcc atacttttcc 840

tatacaacgt ctgccgctct caacgtcact actaacgtga cttatagtat tactaccgcc 900

gcaaggcggg tttccacgtc tacaattgct tatcgtcctg atagcagctt tatgaagtcc 960

attatggcca cacagttaag ggacctagca acgtgggtgt ataccactct acgttaccgg 1020

caaaatcctt tttgtgaacc aagccgcaac cgaaccgccg tgtcagaatt tatgaaaaac 1080

acgcacgtac taatccgtaa cgaaacgccg tacactattt acggtactct cgacatgagc 1140

tccttatatt acaacgaaac catgttcgtg gaaaacaaaa cagcttccga tagtaacaaa 1200

actacaccta cgtcaccatc aatggggttt cagagaacat ttatagatcc cctgtgggac 1260

tatctagact cgctgctgtt tctagatgag attcgtaact ttagcctccg gtcacccacg 1320

tatgtaaacc ttaccccgcc ggaacaccgc cgggctgtaa atctgtccac cctcaatagc 1380

ctttggtggt ggttgcagta a 1401

<210> 34

<211> 1392

<212> DNA

<213> human herpesvirus 5 strain DM7

<220>

<223> AF531334.1 human herpesvirus 5 strain DM7 UL74 gO1b glycoprotein

Gene

<400> 34

atggggagaa aaggagagat gagaggtgtt tttaatttat ttttccttat gtcgctaact 60

ttcctgctat tctctttcat aaactgtagg gctgcggtaa gattatccgt aggacgttac 120

tggtcaggta aagtactgtc tacgataggc aagcaaagac tagacaagtt caaattagag 180

attttgaaac aactagaaaa ggatatctat acgaaatact ttaatatgac cagacaacac 240

attaaaaatc tgactatgaa catgaccgag tttccacggt attacatttt agcgggaccc 300

attcaaaata acagtgttac ctatctttgg ttcgattttt atagcactca gcttcgaaaa 360

ccggctaagt acgttttctc agaatacaat catacggcta aaacaataac attcagaccc 420

ccatcttgcg gtacggtgcc ttccatgact tgtctttccg aaatgctaaa cgtttccaaa 480

cgtaatgata ctggcgaaca aggctgcggc aatttcacca cgttcaaccc catgtttttc 540

aatgtgccac gttggaacac gaagttatat gtaggttcca agaaagtaaa cgtggatagt 600

caaacgatct actttttagg cctaaccgcc ttgcttctac gttacgcgca acgcaactgt 660

acgcacagtt tctacctggt taacgccatg agccgaaatt tatttcgcgt ccctaagtat 720

attaacggta ctaagttgaa aaacactatg cgaaaactca agcgtaaaca agctccagtc 780

aaagaacaat cagaaaaaaa gagtaagaaa tctcaaagta ctactacgcc atattctccc 840

tatacaacgt caaccgctct gaacgtcact actaacgcga cttatagtgt tactaccacc 900

acaaggcggg tttccacgtc tacaattgct tatcgtcctg atagtagctt tatgaagtcc 960

attatgacca cgcaattaag ggacctagcg acgtgggtgt ataccactct acgttaccgg 1020

caaaaccctt tttgtgaatc aagccgcaac cgaaccgccg tatcagaatt tatgaaaaac 1080

acgcacgtac taatccgtaa tgaaacaccg tacactattt acggtactct tgatatgagc 1140

tccttatatt acaacgaaac catgttcgtg gaaaacaaaa cggcttccga aactacacct 1200

acgtcaccat caacgggatt tcagagaacg tttatagatc ccctgtggga ctatctagac 1260

tcgctgctat ttctagatga gatccgtaac tttagtctcc agtcacccac ttatggaaac 1320

cttaccccgc cggaacaccg tcgagctgta aatctgtcca cccttaatag cctttggtgg 1380

tggttgcagt aa 1392

<210> 35

<211> 1395

<212> DNA

<213> human herpesvirus 5 Toledo strain

<220>

<223> AF531355.1 human herpesvirus 5 Toledo UL74 gO1c

Glycoprotein gene

<400> 35

atggggagaa aaggagacat gagaagcatt tctaaattat tctttattat atcactgact 60

gtcctgttat tttctataat aaactgtaag gtcgtcagac caccgggacg ttactggtta 120

ggtacagtac tttctacgat aggcaagcaa aaactagata aattcaagtt agagatttta 180

aaacaattag aaagggaacc ttatacaaaa tacttcaata tgactagaca acacgttaaa 240

aatcttacta tgaatatgac ccagtttcca caatactaca ttctagcagg tcccattcga 300

aacgatagta taacctatct gtggttcgat ttttatagta cccagcttag aaaacccgcc 360

aaatacgtct actcacagta caatcatacg gctaaaacga taacattcag acccccatct 420

tgtggtacag tgccttcaat gacttgtctt tccgaaatgt taaacgtttc caaacgtaat 480

gatactggcg aacaaggctg cggtaatttt accacgttca accccatgtt tttcaatgta 540

ccacgttgga ataccaaatt gtacgtgggt ccgactaaag ttaacgtaga tagtcaaacg 600

atttattttt tgggtttaac cgccctactt ctacgttacg cacaacgcaa ctgcacacac 660

agtttctacc tggttaacgc catgagccgg aatctattcc gcgtccccaa gtatattaac 720

ggcaccaagt tgaaaaacac tatgcgaaaa ctaaaacgta aacaagcgcc agtcaaagaa 780

caattagaaa aaaagactaa aaaatctcag agtactacta cgccatattt ttcctataca 840

acgtctaccg ctctcaacgt cactactaac gcgacttata aggttaccac cagcgcaaag 900

cggattccca catctacgat tgcttatcgt cctgatagca gctttatgaa gtccattatg 960

gccacgcagt taagggatct agcgacatgg gtgtatacta ctctacggta tcggaatgaa 1020

cccttttgta aaccagaccg taaccgtacc gccgtgtcag aatttatgaa aaacacgcac 1080

gtattgattc gtaacgaaac accgtacact atttacggca ctcttgacat gagctcctta 1140

tactacaacg aaaccatgtc cgtggaaaac gaaacggctt ccgataataa cgaaactaca 1200

cctacgtcac catcgacgag gtttcagaaa acgtttatag atcccttatg ggactatcta 1260

gactcgctgc tgtttctaga taaaatccgt aactttagcc tccaattacc cgcgtatgga 1320

aatcttaccc cgccggaaca ccgccgggct gtaaatctat ccaccctcaa tagcctttgg 1380

tggtggtcgc agtaa 1395

<210> 36

<211> 1389

<212> DNA

<213> human herpesvirus 5 PH-BAC isolate

<220>

<223> AC146904.1:119468-120856 human herpesvirus 5 PH-BAC isolate gO2a

Gene UL74

<400> 36

atgtggggaa aaggagagat gagaggtgtt aacttattgt ttcttatatg gctaactttc 60

ctgttgttct ttttcataaa ctgtaagggt gcgcgatcac aacgagcacc atttcgtcct 120

aggatatggc accccacggt attaaaaaaa ctaaagcaat taaaattaga aattttaaga 180

caactagaac ctattcctta cataaagtac ccacaaatca atacgactcg agttcaaagt 240

cttactgtta atatgaccga gtttccttat tattatattt tagcaggtcc tattcgcaac 300

gaaagtgtaa ctcatttgtg gtatgatttc tatagcacac agcttaggaa accagccaaa 360

tatgtatact ctatgtataa tcacacggcc cgaaaaataa cgttcaaacc cccgtcgtgt 420

ggcgcagtgc cttccatgac ttgtctttct gaaatgctaa acgtttccaa gcgtaatgat 480

accggcgaag aaggctgcgg taactttacc acgttcaatc ctatgttttt caatgtaccg 540

cgttggaaca ccaaattgta cgtgggtccg actaaagtta acgtagatag tcaaacgatt 600

tattttttag gtttaaccgc cctgcttcta cgttacgcgc aacgcaactg cacacacagt 660

ttctacctgg ttaacgccat gagccggaat ttatttcgcg tccccaagta tattaacggc 720

accaagttga aaaacactat gcgaaaacta aaacgtaaac aagcgcccgt caaagaacaa 780

ttagaaaaaa agaccaagaa atctcagagt actactacgc catatttgtc ctatacaacg 840

tctaccgctc tcaacgtcac cactaacgtg acttatagtg ttaccaccac cgcaaagcgg 900

gttttcacat ctacgattgc ttatcgtccc gatagcagct ttatgaagtc cattatggcc 960

acgcagttaa gggatctagc gacatgggtg tatactactc tgcgctatcg agatgaacct 1020

ttttgtaaac caaaccgtaa cctgaccgcc gtgtcagagt ttatgaagaa cacgcacgta 1080

ttgatccgta acgaaacacc gtacactatt tatggtactc ttgacatgag ttccttatat 1140

tgtaacgaaa ccatgtccgt ggataacgcg acggctttcg atagtaacaa aacgacaccc 1200

acaccgttac cggggtttca gagaacgttt atagatcccc tgtgggacta tctagactcg 1260

ctgctgttcc tagataaaat ccgtaacttt agcctccagt tacccgggta tggaaatctt 1320

accccgccgg aacaccgccg agctgtaaat ctgtccaccc ttaatagcct ttggtggtgg 1380

ttgcagtaa 1389

<210> 37

<211> 1398

<212> DNA

<213> human herpesvirus 5 strain SW1715

<220>

<223> AF531342.1 human herpesvirus 5 strain SW1715 UL74 gO2b Gene

<400> 37

atggggaaaa aaaaaatact ggtgagaggc gttcctagga tatttatggt atctacattc 60

ctgcttattt ttctcataaa ctgtaaaggt gcgttaaacg tgccccgagg acgtccctgg 120

ataggtaaag taccctcttt aaaatggaaa cttaaagaac aacaattgaa aattgaaatt 180

ttaaagcaat tacagagcga catatacaca aaatatcccc agatcaccaa aaattacact 240

cagtttatta ctacagagct taaaaaattt ccactgtact atatcctagc gggtcctatt 300

cgaaacgaaa gtgtaactca cttgtggttt gatttttata gcactcaact tcgaaaacct 360

gccaaatatg tttactctat gtataatcaa acggctcaga aaatcacgtt taggcccccg 420

ccttgcggta cagtgccttc tatgaattgt ttatccgaga tgttaaatgt ttccaagcgt 480

aatgataccg gcgaagaagg ctgcggtaac ttcaccacgt tcaatcctat gtttttcaat 540

gtaccgcgtt ggaacaccaa attgtacgtg ggtccgacta aagttaacgt agatagtcaa 600

acgatttatt ttctaggttt agccgccctg cttttacgtt acgcgcaacg caactgcaca 660

cgcagtttct acctggttaa cgccatgagc cggaatctat ttcgcgtccc caagtatatt 720

aacggcacca agttaaaaaa cactatgcga aaactaaaac gtaaacaagc gcccgttaaa 780

gaacaattcg aaaaaaagat taagaaatct cagagtagta ctacgccata cttttcctat 840

acaacgtcta ccgctcccaa cgtcactact aacgtgactt acggtgttac aaccaccgca 900

aggcgggttc ccacatctac gatcgcttat cgttctgata gcagctttat gaagtccatt 960

atggccacgc agttaagaga tctagcgacg tgggtgtata ctactttgcg ctatcgggat 1020

gagccttttt gcaaaccaaa ccgtaaccgg accgccgtgt cagaatttat gaaaaacacg 1080

catgtactga tccgtaacga aacaccttac actatttacg gtactctcaa catgagctcc 1140

ttatattaca acgaaaccat gtccgtggaa aacaaaacgg cttccgatag taacaaaact 1200

acacctgcgt caccatcaac agtgtttcag agaacgttta tagaccccct gtgggactat 1260

ctagactcgc tgttatttat aaatgaaatc cgtaacttta gcctccagtc atctgcgtat 1320

agaaacctta cccctccgga acaccgccgg gctgtaaatc tttccaccct caataacctt 1380

tggtggtggt tgcagtaa 1398

<210> 38

<211> 1395

<212> DNA

<213> human herpesvirus 5 strain SW475

<220>

<223> AF531348.1 human herpesvirus 5 strain SW475 UL74 gO3 Gene

<400> 38

atggggagaa aaggagagat gagaggtgtt tttaacttat tgtttcttat atcgttaact 60

tttctgctat tttctctttt gaactgtaag agcgccgcaa gagttttcag actaccgttt 120

ccctatggca gggtattatc aaaaaatggc aggctagctg aaataaagtg gaaacaagaa 180

ctgttaaagc agataggtgc gagccaggat tactataaat tttttaccat tcctactaaa 240

caaggactaa acgctgttgt aacaatggaa cggtttcccg ataactatat cttggctggt 300

cctattcaaa atgatagtat tacctatatg tggttcgatt tctatagtac ccaactgcga 360

aaaccggcca agtacgttta ctcagagtat aatcaaacag gccgaaagat gaggtttaga 420

cctccatctt gtggcactgt gccatctatg ggctgtctat ctgagatgtt gaacgtatcc 480

tttcgtaata acaccggaga agaaagctgt gttaatttga ccacgtttaa tcctatgttt 540

tttaacgtac cacgttggaa cactaaactg tacgttggtt ccactaaagt caatgtggat 600

agtcagacga tctacttttt aggcctagcc gccctgcttc tacgttacgc gcaacgtaac 660

tgcacacgca gtttctacct ggttaacgcc atgagccgaa atctattccg cgttcccaag 720

tatattaacg gcaccaagtt aaaaaacacc atgcgaaagc ttaaacgtaa acaagcaccc 780

gtcaaagaac cgcaaaaaaa gagtaagaaa tctcaaagta ctactacgcc atctttctat 840

acaacgtcta cgactttcaa cgtcaccaac gtgacttata gtgctaccac cactgcacgg 900

cggactccca catctacgat tgcttatcgt cctgatagca gctttatgaa gtccattatg 960

accacacagt taagggactt agcgacgtgg gtatacacca cgctacgcta tcggcaagat 1020

cctttctgta gatcagatcg taatcggacc gccgtgtcag agtttatgaa aaatacgtac 1080

gtattgattc gcaacgaaac accgtacact atttacggca ctcttgacat gagctcctta 1140

tattgcaacg aaaccatgtc cgtggaaaac gaaacggctt ccgataataa cgaaactaca 1200

cctacgtcac catcgacggg gtttcaaaga acgtttatag atcccctgtg ggattaccta 1260

gactcgctgc tgtttctaaa taaaatccgt aactttagcc tccagttacc cgcgtatgga 1320

aaccttaccc cgccggaaca ccgccgggct gtaaatctgt ctaccctcaa tagcctttgg 1380

tggtggttgc agtaa 1395

<210> 39

<211> 1374

<212> DNA

<213> human herpesvirus 5 strain Towne

<220>

<223> AF531356.1 human herpesvirus 5 strain Towne UL74 gO4 gene

<400> 39

atggggagaa agggagagat gagaggtgtt tttaatttat ttttccttat gtcgctaact 60

ttcctgctat tctctttcat aaactgtaag atcacggtag cgcgttttcg agtaaagagt 120

cagaaagcaa aagaggaaga gaggcaacta aaattacgta tactgcaaga actagcgtca 180

aaaacaggtg attattacaa gtttttcaca tttcctagtc agcaaaagtt gtataacata 240

actgtagaaa tgaaacagtt tcccccgaat tccattttag caggacctat tcgtaatcat 300

agcattaccc acctctggtt cgattttcac acgacccaac tccgtaaacc ggccaaatat 360

gtgtattcgg aatataatca tacagggcaa aaaataacat ttcgaccccc atcctgtggt 420

acgatacctt ccatgacttg cctttctgaa atgctaaatg tatcccggcg taacaacacc 480

ggggaggaaa actgtggcaa ttttaccaca tttaatccta tgttttttaa cgtaccacgt 540

tggaacacca aactgtacgt gggtccgagt aaagtcaatg tggatagcca aacaatttat 600

tttttaggtt tagccgccct gcttctacgt tacgcgcaac gtaactgtac acgcagcttc 660

tacctggtta acgccatgag ccggaatata ttccgcgttc ccaagtatat taacagcacc 720

aagctgaaga acactatgcg aaagcttaaa cgtaaacaag cgcctgtcaa atcgatcagt 780

aagaaaagtc gtgttagcac caccacacca tattcttcct acacgtcaac tatttttaac 840

gtcagtacta atgtaactta tagtcctatt gtcccaactc ggattcccac atctacaatt 900

ggttatcgtc ctgacgaaaa ctttatgaaa tccattctga ccacgcagtt aaaagatcta 960

gcgacgtggg tgtatactac tctgcgctat cgagatgaac ctttttgtaa accaaaccgt 1020

aaccggaccg ccgtatcaga atttatgaaa aatacgcacg tattgattcg caacgaaaca 1080

ccgtacacta tttacggtac tcttgacatg agctccttat attacaacga caccatgccc 1140

gtggaaaacg aaacggcttc cgataataac aaaactacac ctacgtcacc atcgacgagg 1200

tttcagagaa cgtttataga tcccatgtgg gattatctag actcgctgct gtttttaagt 1260

gaaatccgta acttcagcct acagtcgtcc acatatggaa accttacccc gccggaacac 1320

cgccgggctg tgaacctgtc caccctcaat agcctttggt ggtggttgca gtaa 1374

<210> 40

<211> 448

<212> DNA

<213> human herpesvirus 5 strain K141

<220>

<223> EU686518.1:14-461 human herpesvirus 5 strain K141 glycoprotein

O5a (UL 74) gene, part of cds shows internal methionine from the gO5 genotype Merlin

Initiation

<400> 40

atgataatgg tgaaaggcat tcctaaaatt atgctcctga tttctataac gttcttgctc 60

ctttccctca taaattgtaa tgtattggta aactccagag gaacaagacg ttcctggccg 120

tataccgtgc tatcttatcg aggtaaagag attctgaaga aacagaagga agatatctta 180

aaacgattga tgtctacatc atctgacgga taccgttttt taatgtaccc cagtcagcaa 240

aaatttcatg ccatcgttat tagcatggat aaatttcctc aagactacat tttagcgggt 300

cccattagaa atgatagcat tacccatatg tggtttgact tttacagtac tcaactccga 360

aaaccagcca agtacgtata ttccgaatat aatcacacgg cccacaaaat aacgttacga 420

cccccacctt gcggcacagt gccttcta 448

<210> 41

<211> 2493

<212> DNA

<213> human herpesvirus 6A Strain U1102

<220>

<223> NC_001664.4:c62129-59637 human beta herpesvirus 6A, variant A DNA,

virosome genome, strain U1102 glycoprotein gB U39 gene

<400> 41

atgagcaaga tggcagtatt attcctggct gtctttttga tgaatagtgt tttaatgata 60

tattgtgatc cggatcatta tatcagagcg ggctataatc acaaatatcc ttttcggatt 120

tgttcgattg ccaaaggcac ggatttaatg cggttcgaca gagatatttc gtgctcgccg 180

tataagtcta atgcaaagat gtcggagggt tttttcatca tttacaaaac aaatatcgag 240

acctacactt ttccagtgag aacgtataaa aaagagttga cgttccaaag tagttaccgt 300

gatgtgggtg tggtttattt tctggatcgg acggtgatgg gtttggccat gccggtgtac 360

gaagcaaatt tagttaattc tcatgcgcag tgttattccg ccgtagcgat gaaacgaccc 420

gatggtacgg tgtttagtgc ctttcatgag gataataata aaaacaatac tctaaattta 480

tttcctctga atttcaaatc tataactaat aaaagattta tcactacgaa agaaccctac 540

tttgcaaggg gtcctttgtg gctatattct acatcaacgt ctctcaattg tattgtgacg 600

gaggctacgg ctaaggcgaa atacccgttt agttactttg ctttgacgac tggcgaaatc 660

gtggaagggt ctccgttctt caacggttca aacggtaaac attttgcaga gccgttagaa 720

aaattgacaa tcttggaaaa ctatactatg atagaagatc taatgaatgg tatgaatggg 780

gccactacgt tagtgaggaa aatcgctttt ctcgagaaag cggatacttt gttttcttgg 840

gaaatcaagg aagagaatga atcggtgtgt atgctaaagc actggaccac ggtgactcac 900

gggcttcgag cggagacgaa tgagacctat cactttatct ctaaggagtt gacagccgct 960

ttcgtcgccc ccaaggagtc cttaaatctt accgatccga aacaaacgtg tattaagaat 1020

gaatttgaaa aaataattaa tgaagtctat atgtcagatt ataatgatac atatagcatg 1080

aatggtagtt atcaaatttt taagactacg ggagatttga ttttgatttg gcaacctctt 1140

gtgcaaaaat ctcttatgtt tcttgagcag ggttcggaaa aaatacgtag gaggcgagat 1200

gtgggggatg ttaagtctag acatgatatt ctttatgtgc aattacagta tctttatgat 1260

actttgaaag attatatcaa tgatgcattg gggaatttgg cagaatcttg gtgtctcgat 1320

caaaagcgaa cgataacgat gttgcacgaa cttagtaaga ttagtccgtc gagtatcgtg 1380

tctgaggttt acggtcgtcc gatatctgca cagttgcatg gtgacgtgtt agctatctcg 1440

aaatgcatag aggttaatca gtcatccgtt cagcttcata agagtatgcg ggtcgtcgat 1500

gcaaagggag taaggagtga aacgatgtgt tataatcggc ccttggtgac gtttagtttt 1560

gtgaactcga cgcctgaggt tgtccctggc cagctagggt tagataatga aattctgttg 1620

ggtgatcata ggacagagga atgtgaaata cctagtacaa agatcttttt atctggaaat 1680

catgcgcacg tgtataccga ttatacgcat acgaattcga cgcccataga agacattgag 1740

gtattggatg cttttattag actaaaaatc gatcctcttg aaaatgccga ttttaaagta 1800

ctcgatttat attcgccgga cgaattgagt agagcaaacg ttttcgatct agagaatatt 1860

cttcgtgaat ataactcata taagagcgca ctatatacta tagaagctaa aattgctacg 1920

aatacacctt cgtatgttaa tgggattaat tcttttttac aagggcttgg ggctataggc 1980

actggattgg gctcggttat aagtgttacg gcaggagcgc ttggggatat tgtgggtgga 2040

gtggtgtctt ttctaaaaaa tccattcggg ggtggtctca tgttgatttt agcgatagta 2100

gttgttgtga taataattgt ggttttcgtt agacaaagac atgtgcttag taagcctatt 2160

gacatgatgt ttccttatgc caccaatccg gtgactactg tgtccagtgt tacggggacc 2220

actgtcgtca agacacctag tgttaaggat gttgacgggg gcacatctgt tgcggtttcg 2280

gaaaaggagg agggtatggc tgacgtcagt gggcaagtaa gtgacgatga atattcacaa 2340

gaagatgctt taaaaatgct caaggccata aagtccttag acgagtccta cagaagaaaa 2400

ccttcgtctt ctgagtctca tgcctcaaaa cctagtttga tagacaggat caggtataga 2460

ggttataaga gtgtaaatgt agaagaagcg tga 2493

<210> 42

<211> 2085

<212> DNA

<213> human herpesvirus 6A Strain U1102

<220>

<223> NC_001664.4:c80170-78086 human betaherpesvirus 6A virion genome,

strain U1102, glycoprotein gH U48

<400> 42

atgctcctcc gactctgggt ctttgtcctg ttgactccct gttacggttg gagaccgttg 60

aacatatcga actcgagcca ttgtagaaat ggaaactttg aaaatccaat cgttcgcccc 120

ggctttataa catttaactt ttatacaaaa aacgacactc ggatatatca agtccctaaa 180

tgcttactcg gctccgatat cacataccac ctgtttgatg ccatcaacac gacagaatcg 240

ttaacaaatt atgaaaaacg cgttacacgt ttttatgagc cgccaatgaa cgatatttta 300

agactttctc ctgtaccttc ggtcaaacaa tttaacttag atcgctctat ccaaccgcag 360

gttgtgtatt ccttaaacat gtacccttca cagggaattt attacgtcag ggtcgtagaa 420

gttcgacaga tgcaatacga caacgtttcc tgtaagctgc ctaattctct caaggaacta 480

atatttccag tccaagtcag atgcgctaaa attacgcgct atgtgggcga agacatctat 540

acccatttct ttactccgga ctttatgata ctgtacatcc agaatcccgc gggagatctg 600

actatgatgt acggaaacac caccagcata aactttaaag ccccttataa gaaaagttca 660

ttcatattca aacagacatt gacagacgat ttactattga tagtcgaaaa agacgtaata 720

gatgtacaat accgtttcat atcagatgcg acattcgtag acgaaacgtt gaatgacgta 780

gatgaagtag aagctctact actcaaattt aataacctag gaatccaaac cctattaaga 840

ggagactgta aaaaacccaa ctatgccggc ataccgcaga tgatgtttct ttacggtatc 900

gtacatttct catatagcac aaaaaacaca ggaccaatgc ccgtgttaag agtgttaaag 960

acacacgaaa atctcctgtc catcgactca tttgtcaacc gatgtgtgaa cgtatcggaa 1020

ggtacgttac aatacccaaa aatgaaggaa tttttaaaat acgagccctc ggactatagc 1080

tacataacca aaaacaaatc catttccgta tctacgctgc tcacgtactt agcgacagcg 1140

tacgaatcca atgtaacgat ttccaagtac aagtggactg acattgccaa cactctacaa 1200

aacatctatg aaaaacacat gttttttact aatctgacat tttccgatag ggaaactcta 1260

ttcatgctag ccgaaatagc gaatatcatc cctaccgatg aacgcatgca gaggcacatg 1320

caactactaa ttggaaacct gtgtaacccc gtagaaatag tttcatgggc ccgcatgctt 1380

acagctgaca gggcaccgaa tctagaaaat atttattcgc cttgtgcctc ccccgtacgc 1440

agagatgtga caaattcttt tctaaaaaca gttctcacgt acgcttccct tgaccgttat 1500

cgatcagaca tgatggagat gctatccgta tacagaccgc caaatatgga gagagtagcg 1560

gctattcagt gtctctcccc aagtgaacca gcagcttctc tgactctgcc gaatgtgaca 1620

tttgtaattt ctccctctta cgtgattaaa ggagtgagcc taacaattac aacgacaatt 1680

gtggctacga gtataataat cacagccata cctctcaatt ccacctgcgt ttcaaccaac 1740

tataaatatg caggacaaga tctgcttgtg ctacgaaaca tctcatctca aacatgcgag 1800

ttctgtcaga gcgtagtcat ggaatatgat gatatcgacg gtcccttaca atacatttac 1860

ataaaaaaca tagacgaact aaaaacattg acagatccca acaacaattt acttgttccc 1920

aacaccagga cgcactatct tttgttagcc aaaaacggct ctgtttttga gatgtctgaa 1980

gtcggaatcg atatagacca agtgtctatc atattggtta tcatttatat tctgatcgca 2040

ataattgctt tattcggatt atatagactt atcagattgt gttga 2085

<210> 43

<211> 753

<212> DNA

<213> human herpesvirus 6A Strain U1102

<220>

<223> NC_001664.4:c123457-122705 human beta herpesvirus 6A virions

Genome, strain U1102 glycoprotein gL U82 gene

<400> 43

atggaacttt tactatttgt aatgtcactc atattactaa ccttctcaaa agcaatacct 60

cttttcaacc ataattcttt ctattttgaa aaacttgacg actgtatcgc agctgtaata 120

aactgcacga aatccgaagt gcctctatta ctagaaccaa tctaccagcc tccggcatat 180

aatgaagacg ttatgtcaat actgctacaa cccccgacaa aaaaaaagcc ttttagccgt 240

ataatggtaa ccgatgaatt tctcagcgac ttcttactcc tacaggataa cccagaacaa 300

ctacgcacat tgtttgcgct aataagggac ccagaatctc gggacaactg gctaaacttt 360

ttcaatggct tccagacatg ttcaccttcc gtcggaataa caacctgcat cagagataac 420

tgtagaaaat attcgcccga aaaaattacg tacgtcaata acttttttgt tgataacatt 480

gcgggtctcg agtttaacat ttcagaaaac acagacagtt tttacagcaa cattggtttt 540

ttattatact tggagaatcc tgctaaaggc gtcacaaaaa ttattaggtt cccttttaac 600

tctttgactc tttttgatac gattttgaat tgtttaaagt atttccactt gaaaaccgga 660

gtagagctcg acctgctaaa acatatggaa acctacaatt ctaaactacc tttccgaagt 720

tcccgcccta caattctgat tagaaacaca taa 753

<210> 44

<211> 1956

<212> DNA

<213> human herpesvirus 6A Strain U1102

<220>

<223> NC_001664.4:c77919-75964 human beta herpesvirus 6A virion genome,

strain U1102 gO U47 gene

<400> 44

atgcatttgg aggtcatcgt ccaatcctat aaaaaaagca aatactattt tagtcacaca 60

ttctacttgt acaaattcat tgtggtcaac tcacccgaca tgcttcacat ctcgcgactc 120

ggcctttttc tgggcctttt cgcgatagtc atgcactccg ttaatctaat aaaatacacg 180

tctgatccct tagaagcttt caaaaccgtc aaccgccaca attggagcga cgaacaaaga 240

gaacattttt acgacctccg aaacttatat acaagttttt gtcagacaaa tctatccctc 300

gactgcttca ctcaaatttt aactaacgtt ttctcttggg acattcgaga ttcacaatgc 360

aagtctgcgg ttagcttgtc tccattacag aatttaccgc ggacagaaat caaaatagtg 420

ctatcctcga cgactgcaaa caaatctatc atcgctagca gtttttctct attttatctt 480

ctgtttgcca cactatctac atataccgca gatccgccat gcgtagagtt actaccattt 540

aaaattctgg gagcacagtt atttgacata aaactaaccg aagaatcctt gcggatggca 600

atgagcaaat tttccaactc gaatctgaca cggtcattga cttccttcac gtcaaaaaac 660

ttctttaatt acaccagctt tgtttacttc ttgctctata acacaacatc atgcgtccct 720

tcaaatgatc aatatttcaa acagtcgcca aaacctataa atgttaccac ttcctttgga 780

cgagccatcg taaactttga ttcgatacta actactacac catcatcgac gtcagcgtct 840

ctcacatcac cacatatccc tagtaccaac ataccaaccc cagcacctcc ccccgtaaca 900

aaaaactcta caaaactgca tacagacacc ataaaagtta caccgaacac acccactata 960

acaacgcaaa caacggaaag catcaaaaaa atagttaaac gttcagattt tcctcgaccc 1020

atgtacaccc caaccgacat tccaactctt acaatccgtc ttaacgccac tattaaaacc 1080

gaacaaaaca ccgaaaaccc aaaaagtcca ccaaaaccaa caaattttga aaataccaca 1140

atcagaattc ccaaaaccct tgagagcgct acagcaacaa caaacgcaac ccaaaagatc 1200

gaaagcacca ccttcacaac aataggaatc aaggaaatta acggcaatac ctattcttca 1260

ccaaaaaact ctatttatct taagagcaaa tcacagcaga gtacaacaaa attcaccgac 1320

gccgaacaca ccactccgat tttaaagttt accacttggc aaaacacggt acgcacatac 1380

atgagtcaca acacagaagt acaaaacatg accgacaaat tccagaggac aaccttgaaa 1440

tcctcaaacg agctacctac cattcagacg ttgtctgtca ctccaaaaca aaaactaccg 1500

tcgaatgtaa ctgccaaaac tgaagtacac ataactaaca acgctttacc atctagtaat 1560

tcatcatact caatcactga agtcactaaa gaggtaaagc atactagaat gtcagcgtcc 1620

actcacgaac agataaacca cacagaaata gcacaaataa caccaattct taacgctcac 1680

acatcggaaa aatcaactac acctcaacgg tccttcaccg ctgaaacgtt cttaacgaca 1740

tcttcaaagc ctaacatcat aacctggtca aacttactaa caacaacgcc taaggaacca 1800

ttaacgaata caagtctaag gtggacagat catatcacaa cacagctaac gactagcaat 1860

agaactcaat cagccaaact aacaaaagct aacatctcgt cacaaacgac taacatctac 1920

ccccaaacaa tcacgggacg atctacagag gtttaa 1956

<210> 45

<211> 2493

<212> DNA

<213> human herpesvirus 6B Strain Z29

<220>

<223> NC-000898.1:c63200-60708 human herpesvirus 6B, strain Z29 genome

gB U39 gene

<400> 45

atgagcaaga tgagagtatt attcctggct gtctttttga tgaatagtgt tttaatgata 60

tattgcgatt cggatgatta tatcagagcg ggctataatc acaaatatcc ttttcggatt 120

tgttcgattg ccaaaggcac tgatttgatg cggttcgaca gagatatttc gtgttcgcca 180

tataagtcta atgcaaagat gtcggagggt tttttcatca tttacaaaac aaatatcgag 240

acctacactt ttccagtgag aacatataaa aacgagctga cgttcccaac cagttaccgt 300

gatgtgggtg tggtttattt tctggatcgg acggtgatgg gtttggccat gccggtgtac 360

gaagcaaatt tagttaattc tcgtgcgcag tgttattcag ccgtagcgat aaaacgaccc 420

gatggtacgg tgtttagtgc ctatcatgag gataataata aaaacgaaac tctagaatta 480

tttcctctga atttcaagtc tgttactaat aaaagattta tcactacgaa agaaccctac 540

tttgcaaggg gtcctttgtg gctctattct acatcgacgt ctctcaattg tattgtgacg 600

gaggctacgg ctaaggcgaa atatccgttt agttactttg ctttgacgac tggtgaaatc 660

gtggaagggt ctccgttctt cgacggttca aacggtaaac attttgcaga gccgttagaa 720

aaattgacaa tcttggaaaa ctatactatg atagaagatc taatgaatgg tatgaatggg 780

gctactacgt tagtaaggaa gatcgctttt ctggagaaag gggatacttt gttttcttgg 840

gaaatcaagg aagagaatga atcggtgtgt atgctaaagc actggactac ggtgactcac 900

gggcttcgag cggagacgga tgagacttat cactttattt ctaaggagtt gacagccgct 960

ttcgtcgcct ccaaggagtc tttaaatctt accgatccca aacaaacgtg tattaagaat 1020

gaatttgaga agataattac agatgtctat atgtcagatt ataatgatgc atacagcatg 1080

aacggtagtt atcaaatttt taagactacg ggagatctga ttttgatttg gcagcctctt 1140

gtgcaaaaat ctcttatggt tcttgagcag ggttcagtaa acttacgtag gaggcgagat 1200

ttggtggatg tcaagtctag acatgatatt ctttatgtgc aattacagta cctctatgat 1260

actttgaaag attatatcaa cgatgccttg gggaatttgg cagaatcttg gtgcctcgat 1320

caaaaacgaa cgataacgat gttgcacgaa cttagtaaga tcagtccatc gagtatcgtg 1380

tctgaggttt acggtcgtcc gatatctgca cagttgcatg gtgatgtgtt agctatctcg 1440

aaatgcatag aagttaatca atcatccgtt cagctttata agagtatgcg ggtcgtcgat 1500

gcgaagggag taaggagtga aacgatgtgt tataatcggc ccttggtgac gtttagcttt 1560

gtgaactcca cgcctgaggt tgtccttggt cagctagggt tagataatga gattctgttg 1620

ggtgatcata ggacagagga atgtgagata cctagtacaa agatatttct atctggaaat 1680

catgcacacg tgtataccga ttatacgcat acgaattcga cgcccataga agacattgag 1740

gtattggatg cttttattag actaaagatc gaccctctcg aaaatgctga ttttaaacta 1800

cttgatttat attcgccgga cgaattgagt agagcaaacg ttttcgattt agagaatatt 1860

cttcgtgaat ataactcata taagagcgca ctatatacta tagaagctaa aattgctact 1920

aatacgccgt cgtatgtcaa tgggattaat tcttttttac aagggcttgg ggctataggc 1980

actggattgg gctcggttat aagtgttacg gcaggagcac ttggggatat tgtgggtgga 2040

gtggtgtctt ttttaaaaaa tccattcggg ggtggtctca tgttgatttt agcgatagta 2100

gttgtcgtta taataattgt ggttttcgtt agacaaaaac atgtgcttag taagcctatt 2160

gacatgatgt ttccttatgc caccaatccg gtgactactg tgtccagtgt tacggggacc 2220

actgtcgtca agacgcctag tgttaaagat gctgacgggg gcacatctgt tgcggtttcg 2280

gaaaaagagg agggtatggc tgacgtcagt ggacaaataa gtggtgatga atattcacaa 2340

gaagatgctt taaaaatgct caaggccata aagtctttag acgagtccta cagaagaaaa 2400

ccttcgtctt ctgagtctca tgcctcaaaa cctagtttga tagacaggat caggtataga 2460

ggttataaga gtgtaaatgt agaagaagcg tga 2493

<210> 46

<211> 2085

<212> DNA

<213> human herpesvirus 6B Strain Z29

<220>

<223> NC-000898.1:c81349-79265 human herpesvirus 6B, strain Z29 genome

gH U48 gene

<400> 46

atgctcttcc gactctgggt ctttgttctg ttgactccct gttacagttg gagaccgtgg 60

accatatcgg acgagagcca ttgtaaaaat ggaaactctg aaaatccaat tgttcgcccg 120

ggctttataa cttttaactt ttatacaaaa aacgacactc ggatatatca agtccctaaa 180

tgcttactcg gatccgatat cacgtaccat ctgtttgatg ccatcaacac gacagaatcg 240

ttaaccaatt atgaaaaacg cgtcacacgt ttctatgagc cgccaatgaa cgatatttta 300

agactttcta ccgtacctgc ggtcaagcaa tttaacctgg atcactctat ccaaccgcag 360

attgtctatt ccttaaacct gtacccttca cacggaattt attacatcag ggttgtggaa 420

gtccgacaga tgcaatacga caacgtttcc tgtaagctgc ctaattctct caacgaactg 480

atctttccag tccaagttag atgcgctaaa attacacgct atgcgggcga aaacatctat 540

acccatttct ttactccgga ctttatgata ctgtacatcc aaaatcccgc aggagatctg 600

actatgatgt atggaaatac caccgacata aactttaaag ccccttatag gaaaagttca 660

ttcatattca aacagacatt gacagacgat ctactattga tagtcgaaaa agacgtagtc 720

gatgaagaat accgtttcat atcagatgcg acattcgtag acgaaacgtt ggatgacgta 780

gatgaagtag aagctctact actcaaattt aataacctag gaatccaaac cctattaagg 840

ggagactgta aaaaacccga ctatgccggc ataccgcaga tgatgtttct ttacggtatc 900

gtacatttct catatagcac aaaaaacaca ggaccgatgc ccgtgttaag agtgttaaag 960

acacacgaaa atctcttgtc catcgactca tttgtcaacc gatgtgtgaa cgtctcggaa 1020

ggtacgatac aatacccaaa aatgaaggaa tttttaaaat acgagccctc ggactatagc 1080

tacatcacca aaaacaaatc cattcccgta tctacgctgc tcacgtactt agcgacagcg 1140

tacgaaacca atgtaacgat ttccaggtac aagtggtctg acattgccaa cactctacaa 1200

aagatctatg aaaaacacat gttttttacg aatctgacat tttccgatag ggaaactcta 1260

ttcatgctag ccgaaatagc gaatttcatc cctgccgatg aacgcatgca gaggcacatg 1320

caactactaa ttggaaacct gtgtaacccc gtagaaatag tttcatgggc ccacatgctt 1380

acagctgaca aggcaccgaa tctagaaaat atttattcgc cttgtgcctc tcccgtacgc 1440

agagatgtaa caaattcttt tgtaaaaaca gttctcacgt acgcttccct cgaccgttat 1500

cgatcagaca tgatggagat gctatccgta tacagaccgc cagatatggc gagagtagcg 1560

gccattcagt gtctctctcc aagtgagcca gcagcttctc tgcctctgcc gaatgtgaca 1620

tttgtaattt ctccctctta tgtgattaaa ggagtgagtt taacaattac aacgacaatc 1680

gtggctacga gtataataat cacagccata cctctcaatt ctacctgcgt ttcaacaaat 1740

tataaatatg caggacaaga tctgcttgtg ctacgaaaca tatcatctca aacatgcgag 1800

ttttgtcaga gcgtagtcat ggaatatgat gatatcgacg gtcccttaca atacatctac 1860

ataaaaaaca tagacgaact aaaaacactg accgatccca acaacaattt acttgttccc 1920

aacaccagga cgcactacct tttgttagcc aaaaacggct ctgtttttga gatgtctgaa 1980

gtcggaatcg atatagacca agtatctatc atattggtta tcatttatgt tctgatcgca 2040

ataattgctt tattcggctt atatagactc atcagattgt gttga 2085

<210> 47

<211> 753

<212> DNA

<213> human herpesvirus 6B Strain Z29

<220>

<223> NC-000898.1:c124745-123993 human herpesvirus 6B, strain Z29 gL

U82 gene

<400> 47

atggaacttt tactatttgt aatgtcactc atattactaa ccttctcgaa agcgatgcct 60

cttttcgacc acaattcttt ctattttgaa aaacttgacg actgtatcgc agctgtaata 120

aattgcacga gatccgaagt acctctatta ctagaaccaa tctaccagcc tccggtatat 180

aatgaagacg ttatgtcaat actgctaaaa cccccaacaa aaaaaaagcc ttttagccgt 240

ataatggtaa ccaatgaatt cctcagcgac ttcttacttc tgcaggataa cccagagcaa 300

ctacgcacat tgtttgcgct gataggggac ccagaatctc gggacaattg gctaaacttt 360

ttcaatggct tccagacatg ttcgccttcc gtcggaataa caacctgcat cagcgataac 420

tgtagaaaat atttgcctga aagaattacg tacgtcaata acttttttgt tgataacatt 480

gcaggtctcg agtttaacat ttcagaaaac acagacagtt tttacagcaa cattggtttt 540

ttattatact tggagaatcc tgctacaggc atcacaaaaa ttatcaggtt cccttttaac 600

tctttgactc tctttgatac gattttgaat tgtttaaagt atttccactt gaaaaccgga 660

gtagaattcg acctgctaaa acagatggaa gcctacaatt ctaaactacc tttccgaagt 720

tcccgcccta cgattctgat tagaaacaca taa 753

<210> 48

<211> 2217

<212> DNA

<213> human herpesvirus 6B Strain Z29

<220>

<223> NC-000898.1:c78999-76783 human herpesvirus 6B, strain Z29

Glycoprotein gO U47 gene

<400> 48

atgcttcaca tctcgcgact cggccttttt ctggcccttt tcgcgatagt catgcactcc 60

gttaatctaa taaaatacac atctgatccc ttagaagctt tcaaaaccgt caaccgccac 120

aattggagcg acgaacaaag agaacatttt tacgacctcc gaaacttgta tacaactttt 180

tgtcagagaa atctatccct cgactgcttc actcaaattt taactaacgt tttctcttgg 240

aacattcgag atttacaatg caagtctgcg gttaacttgt ctccattaca gaatttaccg 300

cgggcagaaa ccaaaatagt gctatcctca acagctgcaa acaaatctat cgtcgctagc 360

agtttttctc tattttatct tctgtttgcc acactatcta catataccgc agatccacca 420

tgcgtagagc tactaccgtt taaaattctg ggaacacagt tatttgacat aaaactgacc 480

gacgaatcct tgcagatggc aatcagtaaa ttttccaact cgaatctgac acggtcattg 540

actccgttca ctcctgaaat cttctttaat tacaccagct ttgtttactt cttgctctat 600

aacacaacat catgcatccg ttcaaatgat caatatttcg aacattcgcc aaaacctata 660

aatgttacca cttcctttgg acgagccatc gtaaactttc attcgatact gactacgacg 720

ccatcatcga cgccatcatc gacgtcagcg tctatcacat caccacatat ccctagtacc 780

aacacaccaa ccccagaacc ttcccccgta acaaaaaact ttacagaatt gcagacagac 840

accataaaag ttacaccgaa cacacccacc ataacagcgc aaacaacgga aagcatcaaa 900

aaagtagtta aacgttcaga ttttcctcga ccgatgtaca ccccgactga cattccaact 960

cttacaatcc gtcgtaacgc cactattaaa accgaacaaa acaccgaaaa ccctaccgaa 1020

aacccaaaaa gtccaccaaa accaacaaat tttgaaaata ccacaatcag aattcccgaa 1080

acgtttgaga gcactacagt ggcaacaaac acgactcaaa agctcgaaag caccaccttc 1140

gcaacaacaa taggaatcga ggaaattagc gacaatatct attcttcacc aaaaaactct 1200

atttatctta agagcaaatc acagcagagc acgacaaaat tcaccgacac cgaacacacc 1260

actccgattt taaagtttac cacttggcaa gacgcggcgc gcacatacat gagccacaac 1320

acggaagtac aaaacatgac cgaaaatttt attaaaattt ctcttggaga aacgatggga 1380

atcacgccta aagaacccac aaatcctacc caacttctca acgtaaaaaa ccaaacagaa 1440

tacgcaaacg aaacccatag cacagaagtg cagaccgtca aaaccttcaa agaggacaga 1500

ttccagagga caactttgaa atcctcaagc gagccaccta ccgttcagac gttgtctgtc 1560

actccaaaaa aaaaactacc gtcaaatgta actgccaaaa ctgaagtaca ggtaactaac 1620

aatgctttac catctagtaa ttcatcacac tcaatcacta aagtcaccga agaaccaaag 1680

caaaatagaa tgtcggcgtc cactcacgga gagatcaacc acacagaaat accacgaatg 1740

acaccaattc ttaacgctca cacatgggaa aaatcgacta cacctcaatg gcccttcacc 1800

gctgaaacgt ccttaacgac atcttcaaag tctgccattc taacctggtc aaacttacta 1860

acaacgccaa aggaaccatt aacgaataca agtctaaggt cgacaaatca tatcacaaca 1920

cagctaacga ctagcaacag aactcaatca gccaaactaa caaaagctca cgtctcgtca 1980

caaacgacta acatctaccc ccaaacaatc acggaacgat ctacggacgt taaaaaaaaa 2040

agttccacag aaagtcggga agctaacaaa actctgcctg gaaacgacta ccgcgtcacc 2100

gataaaaact cacacaacca tccagataac ctcactacca aagcatactc aacccaaaat 2160

gcaacgcatt acacatacaa cgaacgacac gatttaaaca acacagatag cacataa 2217

<210> 49

<211> 2469

<212> DNA

<213> human herpesvirus 7

<220>

<223> NC_001716.2:c61093-58625 human herpesvirus 7 genome, glycoprotein

gB U39

<400> 49

atgaaaattc tattcctgag tgtttttata acttttagct tacagctatc tctacaaaca 60

gaagctgact ttgtcatgac tggacacaat cagcatttac catttcgaat ttgttcaatt 120

gccaccggga cagatttagt gcgttttgac agggaggttt cttgcgcgtc ttacggctct 180

aacattaaaa ctaccgaagg tattttgata atttacaaaa caaagattga agcacacacg 240

ttttctgtca gaacttttaa aaaagaactt acatttcaaa caacatatcg cgatgttggc 300

actgtgtatt tcttagatcg aactgttaca actttgccaa tgccaattga agaagtgcac 360

atggtaaaca ccgaggcgcg ttgtttgtcc tctatctctg taaaacgttc ggaggaagag 420

gagtatgttg catatcataa agatgaatat gtgaataaaa cgttggattt gattccgtta 480

aattttaaat ctgatactgt cagaagatat ataactacta aagaaccatt tttaagaaat 540

ggtcccctct ggttctattc aacatctaca tcgataaatt gcatagttac agactgcatt 600

gcaaagacta aatatccttt tgattttttt gctttatcaa caggggaaac cgtggaaggg 660

tcaccgtttt ataatggtat taattctaaa acatttaatg aaccaacgga aaaaattttg 720

tttagaaata attatactat gctgaaaacg tttgatgatg gatcaaaagg aaattttgtg 780

acgttaacta aaatggcttt tctggaaaag ggaaatacta ttttttcatg ggaagtgcag 840

aatgaagagt cttccatttg tttgttaaag cattggatga caatcccaca cgctttacgg 900

gcagaaaatg ctaacagttt tcactttatt gcgcaggaac taactgcttc ttttgtcaca 960

ggaaaaagta attatacgct ttctgattca aaatataatt gtattaacag caattatact 1020

tcaattttgg atgagattta ccaaacgcaa tacaacaatt cgcatgacaa aaatggtagt 1080

tatgaaattt ttaaaactga gggagattta attctgattt ggcaaccgtt aatacaacgg 1140

aaattaacgg ttttggaaaa tttttctaat gcttctagaa aaaggaggaa gagggaatta 1200

gagactaaca aagacatcgt atatgttcaa ctacaatacc tatacgacac tctgaaagat 1260

tacattaaca cagcactagg taagcttgct gaagcctggt gtttagatca aaaacgcact 1320

atcacagtgt tgcacgagct tagtaaaata agtccttctg gaatcatttc agcagtgtac 1380

ggtaaaccca tgtccgctaa attaattggt gatgtattag cagtctcaaa gtgcattgaa 1440

gtcaaccaga cttctgttca gctacataaa agtatgagat tgacaaaaga ttcaagttac 1500

gatgctctaa gatgttattc tcggccattg ttaacatatt catttgcaaa ttcttcgaag 1560

gaaacttatt taggacaact tggtttagac aatgagatat tactgggaaa tcacagaaca 1620

gaagaatgtg aacaatctaa cacgaaaatt tttttgtctg gtaaattcgc tcatattttt 1680

aaagactata cgtacgttaa ttctagtttg ataacagaaa tagaagcttt agatgcgttt 1740

gttgacttaa acatagatcc tttagaaaat gcagatttta cattattgga attgtataca 1800

aaagatgaac tgagcaaagc gaacgttttt gatttggaaa ccattcttag agaatacaat 1860

tcttacaaaa gtgcgctaca ccatatagaa acaaaaattg caactgttac tccaacatat 1920

ataggaggga ttgacacatt tttcaaaggt cttggcgctc ttggtcttgg tttgggggct 1980

gtgctgggtg taacggctgg tgctttggga gatgtggtga atggagtttt ctcttttctt 2040

aaaaatccat ttggtggagc actaactatc ttactaactt tgggagtgat tggcttagtt 2100

attttcttat ttttaagaca taaacgatta gcacaaacac cgattgatat tttatttcct 2160

tatacatcaa aatcaacaaa ttcggtactt caagcaacgc aatcagttca agcgcaagtg 2220

aaagaacctt tagattcatc tccgccttat ttaaaaacta acaaagacac agaaccgcaa 2280

ggtgatgaca taacacacac taatgaatat tcacaagtgg aagctttaaa aatgttgaaa 2340

gctattaaat tattagatga gtcatataaa aaagcggaaa tcgctgaggc aaaaaaatca 2400

cagagaccaa gcctacttga aaggattcaa tacaggggct atcagaaact ttcaacagaa 2460

gaactgtga 2469

<210> 50

<211> 2073

<212> DNA

<213> human herpesvirus 7

<220>

<223> NC_001716.2:c77113-75041 human herpesvirus 7 genomic glycoprotein

gH U48 gene

<400> 50

atgtattttt acataaatag tctacttctc atcgtgtcaa taaatggatg gaaacactgg 60

aatatactca attcttcaat ttgcgtaaat gaaaaaacaa atcaaactat tattcaacct 120

ggtttaataa cgtttaattt ccatgattat aacgaaactc gggtttatca gattcccaaa 180

tgcttattcg gatatacttt tgtctcgaat ttatttgatt ctgtgaattt cgatgaatca 240

tttgatcaat ataaacatcg gattacacgt ttttttaacc catcaacaga gaaagctgtg 300

aaaatctatg cacaaaaatt tcagacaaat atcaaacctg tttcgcatac aaaaacgatt 360

acagtgtctt tattaccttt attttatgaa aaggatgtct actttgcaaa tgtttcggaa 420

attcgcaaac tctattacaa ccaatacatt tgcacacttt caaatggctt gactgattat 480

ctattcccaa taacagaaag atgtgttatg agacattata attacttaaa tactgtgttc 540

atgctagctt tgacaccatc gttttttata atttcagtgg aaacaggaat ggatgatgtc 600

gtttttatct ttggaaatgt tagtcgtatt ttttttaaag caccttttcg aaaaagttca 660

ttcatatata gacagactgt ctcagacgat ctcctgttaa ttacaaaaaa aacaacaatt 720

gaaagatttt atccgtttct caaaatagac tttctggatg atatttggaa acaaaattat 780

gacatctcgt ttttaatagc caaattcaat aagttagcaa ctgtttatat catggaggga 840

ttttgcggaa aaccagttaa caaagacaca ttccatttaa tgtttttatt cggcttaact 900

cattttctat atagtactcg aggagatgga ctcctccctc tgttggaaat ccttaatact 960

caccaaagca tcattacgat gggtaggttt ttagaaaagt gcttcaaaat gactaagagt 1020

catttattat atcctgagat ggaaaaactt cagaatttcc agttagtaga ttattcttat 1080

attacatctg atctgacaat tcctatctct gctaagctag catttttatc tttagcagat 1140

ggaagaatcg ttacagttcc acaaaacaaa tggaaagaaa tagaaaacaa tattgaaaca 1200

ttatatgaaa aacataaatt gtttacaaat ttaacccaac cggaacgtgc aaatttgttt 1260

ttactctcag aaattggaaa cagtctagtc ttccaagaaa agatcaagcg aaagattcat 1320

gttttgctcg caagtctgtg caatcctttg gaaatgtatt tttggacaca tatgcttgat 1380

aatgtcatgg acattgaaac gatgttttct ccttgtgcaa cagccacgcg caaagattta 1440

actcaaagag ttgtcaacaa cattttatcc tataaaaacc tagacgcata cacaaacaag 1500

gtgatgaaca cactttctgt atatagaaaa aagagattag atatgtttaa aagcatttcc 1560

tgtgtttcaa atgaacaagc tgccttcctc acattaccaa atattactta caccatctct 1620

tcaaaatata ttttagccgg tactagtttc agtgtcacga gtactgtcat aagcactaca 1680

attattatca ctgttgttcc cttaaactct acctgcacac ctactaatta taaatattcg 1740

gtgaaaaata taaaaccaat ctataatatt tcatcccacg attgtgtgtt ttgtgaaagc 1800

ttggttgtgg aatatgacga catagacgga attatccaat ttgtatacat aatggatgac 1860

aagcaactat taaaattaat agatccggac acaaatttta tcgatgtgaa tccacgaaca 1920

cattatttat tgtttttaag aaatggctct gttttcgaaa ttaccgcatt agatctaaaa 1980

tcaagtcaag tttcaatcat gttagttctt ctgtatttaa ttatcataat tatagttttg 2040

tttggtattt atcatgtatt tagattgttt tga 2073

<210> 51

<211> 741

<212> DNA

<213> human herpesvirus 7

<220>

<223> NC_001716.2: c121009-120269 human herpesvirus 7 genome,

glycoprotein gL U82

<400> 51

atgaaaacta acatcttttt tatatttctt atctccattc taaaccaaat atatgcttta 60

tttaataact cttattattc taatttagaa caagaatgta tcaaaaacat tctaaattgt 120

acccaatcaa aaactctgtc gcttctggaa cctattgatc aggcacctat accaaattcg 180

gatataattt ctcgcttatt atatcatact ccctatatct caaggagaga tcaagtttta 240

attgatgaag attttttaga aacattttac ctactgtata ataatcctaa tcaactacac 300

accttacttt ccttaattaa agattcagaa tcagggcaca actggcttgg ctttttaaat 360

aactttgaaa gatgtctttc agataacaca cttttaacct gtagagataa tgtgtgtaaa 420

tcatactctt atgaaaaact caaattcacg ggcaacatct ttgtagaaaa tataatcgga 480

tttgaattca atataccatc aaatatgata aattttaaca tgtcaatttt gatttacctt 540

gaaaatgaag agactcgcac acagagaatt gtgagaattg atcaccatgg aattaatgtt 600

tttgatgctt tgttaaattg tttgagatat ttttctaggt attacaactt tagtttcccg 660

ttaattcaag aaatggaaaa atataatgaa gtgcttccat tccgaagcga gttttcgaat 720

ttgctcatta gaacttactg a 741

<210> 52

<211> 942

<212> DNA

<213> human herpesvirus 7

<220>

<223> NC_001716.2:c74803-73862 human herpesvirus 7 genome, glycoprotein

gO U47 gene

<400> 52

atgaaaaaca aaatgtattc aatgctagtg ttcacgttga tttcttttct tttttatagt 60

tatctgatca tatggactcc tgtattaagt gtttgctctg aaaaaatctc gtttgtaaat 120

ttaacgaatt tttccatgtg gccgaaattc gcaaaatttc attatgagtc ttttgaaaaa 180

acatatattc agagttgcga catacccatc tctaagaact gttttaaaca gattttattt 240

tggtcattcc gtctatccca gaaaaagaat atttgccttt ctaaaataaa tatgctctat 300

ctagataatt ttccgcgatg gacattacat tttgaatttc ccactaaaac aaacagaaaa 360

cgtcacgttt acttagataa tatttccttt ttgtatttag tttttgctac actagcattc 420

aaaacgatgg atgactcttg tgtcaataaa ataccgtttg aagtacttgc ttcacatttg 480

tttaaaatta actttagcca aaacaagatt gaaaccattt tccaagatct ccaaaaccat 540

actgaagctc aattattttc acgcgaaaat tctgagcaac ttttttcttt tacgaatttt 600

atttactact ttgtttacaa tcgaacagat tgcaagaatt ctatttcaaa atttttctat 660

aattctgtga acacgcggaa tgtgtcaaca ccatttggtg ttaccaactt ctccttggta 720

aggggaatca tgtcaccaat acaaagtttt aaggggaact tgatgttctt agaaaataag 780

accaaagtta ctaagcctac agcaattccg aacgctgtta cttccgaacc aacaaaattt 840

tttccatcta ctcgaggcac ctcaagcatg caagcttcac aacagacttc atcatttcct 900

acgacctttt tcacgacaaa ccatagtaac acaagcacat aa 942

<210> 53

<211> 689

<212> DNA

<213> human herpesvirus 8 strain GK18

<220>

<223> NC_009333.1:76014-76437, 76532-76794 human herpesvirus 8 strain

GK18 genomic glycoprotein K8.1 with a transmembrane domain

<400> 53

atgagttcca cacagattcg cacagaaatc cctgtggcgc tcctaatcct atgcctttgt 60

ctggtggcgt gccatgccaa ttgtcccacg tatcgttcgc atttgggatt ctggcaagag 120

ggttggagtg gacaggttta tcaggactgg ctaggcagga tgaactgttc ctacgagaat 180

atgacggccc tagaggccgt ctccctaaac gggaccagac tagcagctgg atctccgtcg 240

agtgagtatc caaatgtctc cgtatctgtt gaagatacgt ctgcctctgg gtctggagaa 300

gatgcaatag atgaatcggg gtcgggggag gaagagcgtc ccgtgacctc ccacgtgact 360

tttatgacac aaagcgtcca ggccaccaca gaactgaccg atgccttaat atcagccttt 420

tcaggatcat attcatctgg ggaaccatcc aggaccacgc gaattcgcgt atcaccggtc 480

gcagaaaacg gcagaaatag tggtgctagt aaccgtgtgc cattttctgc caccactaca 540

acgactagag gaagagacgc gcactacaat gcagaaatac ggacccatct ttacatacta 600

tgggctgtgg gtttattgct gggacttgtc cttatacttt acctgtgcgt tccacgatgc 660

cggcgtaaga aaccctacat agtgtaaca 689

<210> 54

<211> 504

<212> DNA

<213> human herpesvirus 8

<220>

<223> AF068830.1 1-504 Kaposi's sarcoma-associated herpesvirus

Glycoprotein K8.1B mRNA, complete cds BCBL1 strain

<400> 54

atgagttcca cacagattcg cacagaaatc cctgtggcgc tcctaatcct atgcctttgt 60

ctggtggcgt gccatgccaa ttgtcccacg tatcgttcgc atttgggatt ctggcaagag 120

ggttggagtg gacaggttta tcaggactgg ctaggcagga tgaactgttc ctacgagaat 180

atgacggccc tagaggccgt ctccctaaac gggaccagac tagcagctgg atctccgtcg 240

agatcatatt catctgggga accatccagg accacgcgaa ttcgcgtatc accggtcgca 300

gaaaacggca gaaatagtgg tgctagtaac cgtgtgccat tttctgccac cactacaacg 360

actagaggaa gagacgcgca ctacaatgca gaaatacgga cccatcttta catactatgg 420

gctgtgggtt tattgctggg acttgtcctt atactttacc tgtgcgttcc acgatgccgg 480

cgtaagaaac cctacatagt gtaa 504

<210> 55

<211> 687

<212> DNA

<213> human herpesvirus 8

<220>

<223> AF068829.1 1-687 Kaposi's sarcoma-associated herpesvirus

Glycoprotein K8.1A mRNA, intact cds

<400> 55

atgagttcca cacagattcg cacagaaatc cctgtggcgc tcctaatcct atgcctttgt 60

ctggtggcgt gccatgccaa ttgtcccacg tatcgttcgc atttgggatt ctggcaagag 120

ggttggagtg gacaggttta tcaggactgg ctaggcagga tgaactgttc ctacgagaat 180

atgacggccc tagaggccgt ctccctaaac gggaccagac tagcagctgg atctccgtcg 240

agtgagtatc caaatgtctc cgtatctgtc gaagatacgt ctgcctctgg gtctggagaa 300

gatgcaatag atgaatcggg gtcgggggag gaagagcgtc ccgtgacctc tcacgtgact 360

tttatgacac aaagcgtcca ggccaccaca gaactgaccg atgccttaat atcagccttt 420

tcaggatcat attcatctgg ggaaccatcc aggaccacgc gaattcgcgt atcaccggtc 480

gcagaaaacg gcagaaatag tggtgctagt aaccgtgtgc cattttctgc caccactaca 540

acgactagag gaagagacgc gcactacaat gcagaaatac ggacccatct ttacatacta 600

tgggctgtgg gtttattgct gggacttgtc cttatacttt acctgtgcgt tccacgatgc 660

cggcgtaaga aaccctacat agtgtaa 687

<210> 56

<211> 504

<212> DNA

<213> human herpesvirus 8

<220>

<223> AF068830.1 1-504 Kaposi's sarcoma-associated herpesvirus

Glycoprotein K8.1B mRNA, complete cds BCBL1 strain

<400> 56

atgagttcca cacagattcg cacagaaatc cctgtggcgc tcctaatcct atgcctttgt 60

ctggtggcgt gccatgccaa ttgtcccacg tatcgttcgc atttgggatt ctggcaagag 120

ggttggagtg gacaggttta tcaggactgg ctaggcagga tgaactgttc ctacgagaat 180

atgacggccc tagaggccgt ctccctaaac gggaccagac tagcagctgg atctccgtcg 240

agatcatatt catctgggga accatccagg accacgcgaa ttcgcgtatc accggtcgca 300

gaaaacggca gaaatagtgg tgctagtaac cgtgtgccat tttctgccac cactacaacg 360

actagaggaa gagacgcgca ctacaatgca gaaatacgga cccatcttta catactatgg 420

gctgtgggtt tattgctggg acttgtcctt atactttacc tgtgcgttcc acgatgccgg 480

cgtaagaaac cctacatagt gtaa 504

<210> 57

<211> 2538

<212> DNA

<213> human herpesvirus 8 strain GK18

<220>

<223> NC_009333.1:8665-11202 human herpesvirus 8 strain GK18 genome

Glycoprotein gB Gene ORF8

<400> 57

atgactccca ggtctagatt ggccaccctg gggactgtca tcctgttggt ctgcttttgc 60

gcaggcgcgg cgcactcgag gggtgacacc tttcagacgt ccagttcccc cacaccccca 120

ggatcttcct ctaaggcccc caccaaacct ggtgaggaag catctggtcc taagagtgtg 180

gacttttacc agttcagagt gtgtagtgca tcgatcaccg gggagctttt tcggttcaac 240

ctggagcaga cgtgcccaga caccaaagac aagtaccacc aagaaggaat tttactggtg 300

tacaaaaaaa acatagtgcc tcatatcttt aaggtgcggc gctataggaa aattgccacc 360

tctgtcacgg tctacagggg cttgacagag tccgccatca ccaacaagta tgaactcccg 420

agacccgtgc cactctatga gataagccac atggacagca cctatcagtg ctttagttcc 480

atgaaggtaa atgtcaacgg ggtagaaaac acatttactg acagagacga tgttaacacc 540

acagtattcc tccaaccagt agaggggctt acggataaca ttcaaaggta ctttagccag 600

ccggtcatct acgcggaacc cggctggttt cccggcatat acagagttag gaccaccgtc 660

aattgcgaga tagtggacat gatagccagg tctgctgaac catacaatta ctttgtcacg 720

tcactgggtg acacggtgga agtctcccct ttttgctata acgaatcctc atgcagcaca 780

acccccagca acaaaaatgg ccttagcgtc caagtagttc tcaaccacac tgtggtcacg 840

tactctgaca gaggaaccag tcccactccc caaaacagga tctttgtgga aacgggagcg 900

tacacgcttt cgtgggcctc cgagagcaag accacggccg tgtgtccgct ggcactgtgg 960

aaaaccttcc cgcgctccat ccagactacc cacgaggaca gcttccactt tgtggccaac 1020

gagatcacgg ccaccttcac ggctcctcta acgccagtgg ccaactttac cgacacgtac 1080

tcttgtctga cctcggatat caacaccacg ctaaacgcca gcaaggccaa actggcgagc 1140

actcacgtcc ctaacgggac ggtccagtac ttccacacaa caggcggact ctatttggtc 1200

tggcagccca tgtccgcgat taacctgact cacgctcagg gcgacagcgg gaaccccacg 1260

tcatcgccgc ccccctccgc atcccccatg accacctctg ccagccgcag aaagagacgg 1320

tcagccagta ccgctgctgc cggcggcggg gggtccacgg acaacctgtc ttacacgcag 1380

ctgcagtttg cctacgacaa actgcgggat ggcattaatc aggtgttaga agaactctcc 1440

agggcatggt gtcgcgagca ggtcagggac aacctaatgt ggtacgagct cagtaaaatc 1500

aaccccacca gcgttatgac agccatctac ggtcgacctg tatccgccaa gttcgtagga 1560

gacgccattt ccgtgaccga gtgcattaac gtggaccaga gctccgtaaa catccacaag 1620

agcctcagaa ccaatagtaa ggacgtgtgt tacgcgcgcc ccctggtgac gtttaagttt 1680

ttgaacagtt ccaacctatt caccggccag ctgggcgcgc gcaatgagat aatactgacc 1740

aacaaccagg tggaaacctg caaagacacc tgcgaacact acttcatcac ccgcaacgag 1800

actctggtgt ataaggacta cgcgtacctg cgtactataa acaccactga catatccacc 1860

ctgaacactt ttatcgccct gaatctatcc tttattcaaa acatagactt caaggccatc 1920

gagctgtaca gcagtgcaga gaaacgactc gcgagtagcg tgtttgacct ggagacgatg 1980

ttcagggagt acaactacta cacacatcgt ctcgcgggtt tgcgcgagga tctggacaac 2040

accatagata tgaacaagga gcgcttcgta agggacttgt cggagatagt ggcggacctg 2100

ggtggcatcg gaaaaacggt ggtgaacgtg gccagcagcg tggtcactct atgtggctca 2160

ttggttaccg gattcataaa ttttattaaa caccccctag gtggcatgct gatgatcatt 2220

atcgttatag caatcatcct gatcattttt atgctcagtc gccgcaccaa taccatagcc 2280

caggcgccgg tgaagatgat ctaccccgac gtagatcgca gggcacctcc tagcggcgga 2340

gccccaacac gggaggaaat caaaaacatc ctgctgggaa tgcaccagct acaacaagag 2400

gagaggcaga aggcggatga tctgaaaaaa agtacaccct cggtgtttca gcgtaccgca 2460

aacggccttc gtcagcgtct gagaggatat aaacctctga ctcaatcgct agacatcagt 2520

ccggaaacgg gggagtga 2538

<210> 58

<211> 2193

<212> DNA

<213> human herpesvirus 8 strain GK18

<220>

<223> NC_009333.1:37212-39404 human herpesvirus 8 strain GK18 genome

Glycoprotein gH ORF22 gene

<400> 58

atgcagggtc tagccttctt ggcggccctt gcatgctggc gatgcatatc gttgacatgt 60

ggagccactg gcgcgttgcc gacaacggcg acgacaataa cccgctccgc cacgcagctc 120

atcaatggga gaaccaacct ctccatagaa ctggaattca acggcactag tttttttcta 180

aattggcaaa atctgttgaa tgtgatcacg gagccggccc tgacagagtt gtggacctcc 240

gccgaagtcg ccgaggacct cagggtaact ctgaaaaaga ggcaaagtct ttttttcccc 300

aacaagacag ttgtgatctc tggagacggc catcgctata cgtgcgaggt gccgacgtcg 360

tcgcaaactt ataacatcac caagggcttt aactatagcg ctctgcccgg gcaccttggc 420

ggatttggga tcaacgcgcg tctggtactg ggtgatatct tcgcatcaaa atggtcgcta 480

ttcgcgaggg acaccccaga gtatcgggtg ttttacccaa tgaatgtcat ggccgtcaag 540

ttttccatat ccattggcaa caacgagtcc ggcgtagcgc tctatggagt ggtgtcggaa 600

gatttcgtgg tcgtcacgct ccacaacagg tccaaagagg ctaacgagac ggcgtcccat 660

cttctgttcg gtctcccgga ttcactgcca tctctgaagg gccatgccac ctatgatgaa 720

ctcacgttcg cccgaaacgc aaaatatgcg ctagtggcga tcctgcctaa agattcttac 780

cagacactcc ttacagagaa ttacactcgc atatttctga acatgacgga gtcgacgccc 840

ctcgagttca cgcggacgat ccagaccagg atcgtatcaa tcgaggccag gcgcgcctgc 900

gcagctcaag aggcggcgcc ggacatattc ttggtgttgt ttcagatgtt ggtggcacac 960

tttcttgttg cgcggggcat tgccgagcac cgatttgtgg aggtggactg cgtgtgtcgg 1020

cagtatgcgg aactgtattt tctccgccgc atctcgcgtc tgtgcatgcc cacgttcacc 1080

actgtcgggt ataaccacac cacccttggc gctgtggccg ccacacaaat agctcgcgtg 1140

tccgccacga agttggccag tttgccccgc tcttcccagg aaacagtgct ggccatggtc 1200

cagcttggcg cccgtgatgg cgccgtccct tcctccattc tggagggcat tgctatggtc 1260

gtcgaacata tgtataccgc ctacacttat gtgtacacac tcggcgatac tgaaagaaaa 1320

ttaatgttgg acatacacac ggtcctcacc gacagctgcc cgcccaaaga ctccggagta 1380

tcagaaaagc tactgagaac atatttgatg ttcacatcaa tgtgtaccaa catagagctg 1440

ggcgaaatga tcgcccgctt ttccaaaccg gacagcctta acatctatag ggcattctcc 1500

ccctgctttc taggactaag gtacgatttg catccagcca agttgcgcgc cgaggcgccg 1560

cagtcgtccg ctctgacgcg gactgccgtt gccagaggaa catcgggatt cgcagaattg 1620

ctccacgcgc tgcacctcga tagcttaaat ttaattccgg cgattaactg ttcaaagatt 1680

acagccgaca agataatagc tacggtaccc ttgcctcacg tcacgtatat catcagttcc 1740

gaagcactct cgaacgctgt tgtctacgag gtgtcggaga tcttcctcaa gagtgccatg 1800

tttatatctg ctatcaaacc cgattgctcc ggctttaact tttctcagat tgataggcac 1860

attcccatag tctacaacat cagcacacca agaagaggtt gccccctttg tgactctgta 1920

atcatgagct acgatgagag cgatggcctg cagtctctca tgtatgtcac taatgaaagg 1980

gtgcagacca acctcttttt agataagtca cctttctttg ataataacaa cctacacatt 2040

cattatttgt ggctgaggga caacgggacc gtagtggaga taaggggcat gtatagaaga 2100

cgcgcagcca gtgctttgtt tctaattctc tcttttattg ggttctcggg ggttatctac 2160

tttctttaca gactgttttc catcctttat tag 2193

<210> 59

<211> 504

<212> DNA

<213> human herpesvirus 8 strain GK18

<220>

<223> NC_009333.1:c70014-69511 human herpesvirus 8 strain GK18 genome,

glycoprotein gL gene ORF47

<400> 59

atggggatct ttgcgctatt tgccgtcctg tggaccaccc tattggtcac atctcacgca 60

tacgtcgcct taccatgttg cgcaattcag gcatcggcag cctctaccct gccgttgttc 120

tttgcggtcc actctatcca cttcgccgat ccgaatcact gcaacggggt ctgtatagcc 180

aagctgcgaa gcaaaacagg cgacattacc gtggaaacat gcgtgaatgg gtttaatctg 240

aggtcatttt tagtcgcggt cgttcgaaga ttggggtcct gggcgtcgca ggaaaacctg 300

aggttgttgt ggtatttaca acgaagtttg acggcctata ctgtaggttt taacgcgacc 360

actgcagata gctctattca caacgtaaac ataattataa taagcgtggg aaaggccatg 420

aaccggacag gttctgttag cggaagtcag actcgggcta aaagcagcag ccggagagcg 480

cacgcaggtc aaaagggaaa ataa 504

<210> 60

<211> 1185

<212> DNA

<213> human herpesvirus 1 strain 17

<220>

<223> NC_001806.2:138423-139607 human herpesvirus 1 strain

17, glycoprotein gD-US6

<400> 60

atgggggggg ctgccgccag gttgggggcc gtgattttgt ttgtcgtcat agtgggcctc 60

catggggtcc gcggcaaata tgccttggtg gatgcctctc tcaagatggc cgaccccaat 120

cgctttcgcg gcaaagacct tccggtcctg gaccagctga ccgaccctcc gggggtccgg 180

cgcgtgtacc acatccaggc gggcctaccg gacccgttcc agccccccag cctcccgatc 240

acggtttact acgccgtgtt ggagcgcgcc tgccgcagcg tgctcctaaa cgcaccgtcg 300

gaggcccccc agattgtccg cggggcctcc gaagacgtcc ggaaacaacc ctacaacctg 360

accatcgctt ggtttcggat gggaggcaac tgtgctatcc ccatcacggt catggagtac 420

accgaatgct cctacaacaa gtctctgggg gcctgtccca tccgaacgca gccccgctgg 480

aactactatg acagcttcag cgccgtcagc gaggataacc tggggttcct gatgcacgcc 540

cccgcgtttg agaccgccgg cacgtacctg cggctcgtga agataaacga ctggacggag 600

attacacagt ttatcctgga gcaccgagcc aagggctcct gtaagtacgc cctcccgctg 660

cgcatccccc cgtcagcctg cctctccccc caggcctacc agcagggggt gacggtggac 720

agcatcggga tgctgccccg cttcatcccc gagaaccagc gcaccgtcgc cgtatacagc 780

ttgaagatcg ccgggtggca cgggcccaag gccccataca cgagcaccct gctgcccccg 840

gagctgtccg agacccccaa cgccacgcag ccagaactcg ccccggaaga ccccgaggat 900

tcggccctct tggaggaccc cgtggggacg gtggcgccgc aaatcccacc aaactggcac 960

ataccgtcga tccaggacgc cgcgacgcct taccatcccc cggccacccc gaacaacatg 1020

ggcctgatcg ccggcgcggt gggcggcagt ctcctggcag ccctggtcat ttgcggaatt 1080

gtgtactgga tgcgccgcca cactcaaaaa gccccaaagc gcatacgcct cccccacatc 1140

cgggaagacg accagccgtc ctcgcaccag cccttgtttt actag 1185

<210> 61

<211> 2715

<212> DNA

<213> human herpesvirus 1 strain 17

<220>

<223> NC_001806.2:c55795-53081 human herpesvirus 1 strain

17, glycoprotein gB-UL27

<400> 61

atgcgccagg gcgcccccgc gcgggggcgc cggtggttcg tcgtatgggc gctcttgggg 60

ttgacgctgg gggtcctggt ggcgtcggcg gctccgagtt cccccggcac gcctggggtc 120

gcggccgcga cccaggcggc gaacgggggc cctgccactc cggcgccgcc cgcccctggc 180

gcccccccaa cgggggaccc gaaaccgaag aagaacaaaa aaccgaaacc cccaaagccg 240

ccgcgccccg ccggcgacaa cgcgaccgtc gccgcgggcc acgccaccct gcgcgagcac 300

ctgcgggaca tcaaggcgga gaacaccgat gcaaactttt acgtgtgccc accccccacg 360

ggcgccacgg tggtgcagtt cgagcagccg cgccgctgcc cgacccggcc cgagggtcag 420

aactacacgg agggcatcgc ggtggtcttc aaggagaaca tcgccccgta caagttcaag 480

gccaccatgt actacaaaga cgtcaccgtt tcgcaggtgt ggttcggcca ccgctactcc 540

cagtttatgg ggatctttga ggaccgcgcc cccgtcccct tcgaggaggt gatcgacaag 600

atcaacgcca agggggtctg tcggtccacg gccaagtacg tgcgcaacaa cctggagacc 660

accgcgtttc accgggacga ccacgagacc gacatggagc tgaaaccggc caacgccgcg 720

acccgcacga gccggggctg gcacaccacc gacctcaagt acaacccctc gcgggtggag 780

gcgttccacc ggtacgggac gacggtaaac tgcatcgtcg aggaggtgga cgcgcgctcg 840

gtgtacccgt acgacgagtt tgtgttggcg actggcgact ttgtgtacat gtccccgttt 900

tacggctacc gggaggggtc gcacaccgaa cacaccagct acgccgccga ccgcttcaag 960

caggtcgacg gcttctacgc gcgcgacctc accaccaagg cccgggccac ggcgccgacc 1020

acccggaacc tgctcacgac ccccaagttc accgtggcct gggactgggt gccaaagcgc 1080

ccgtcggtct gcaccatgac caagtggcag gaggtggacg agatgctgcg ctccgagtac 1140

ggcggctcct tccgattctc ttccgacgcc atatccacca ccttcaccac caacctgacc 1200

gagtacccgc tctcgcgcgt ggacctgggg gactgcatcg gcaaggacgc ccgcgacgcc 1260

atggaccgca tcttcgcccg caggtacaac gcgacgcaca tcaaggtggg ccagccgcag 1320

tactacctgg ccaatggggg ctttctgatc gcgtaccagc cccttctcag caacacgctc 1380

gcggagctgt acgtgcggga acacctccgc gagcagagcc gcaagccccc aaaccccacg 1440

cccccgccgc ccggggccag cgccaacgcg tccgtggagc gcatcaagac cacctcctcc 1500

atcgagttcg ccaggctgca gtttacgtac aaccacatac agcgccatgt caacgatatg 1560

ttgggccgcg ttgccatcgc gtggtgcgag ctgcagaatc acgagctgac cctgtggaac 1620

gaggcccgca agctgaaccc caacgccatc gcctcggcca ccgtgggccg gcgggtgagc 1680

gcgcggatgc tcggcgacgt gatggccgtc tccacgtgcg tgccggtcgc cgcggacaac 1740

gtgatcgtcc aaaactcgat gcgcatcagc tcgcggcccg gggcctgcta cagccgcccc 1800

ctggtcagct ttcggtacga agaccagggc ccgttggtcg aggggcagct gggggagaac 1860

aacgagctgc ggctgacgcg cgatgcgatc gagccgtgca ccgtgggaca ccggcgctac 1920

ttcaccttcg gtgggggcta cgtgtacttc gaggagtacg cgtactccca ccagctgagc 1980

cgcgccgaca tcaccaccgt cagcaccttc atcgacctca acatcaccat gctggaggat 2040

cacgagtttg tccccctgga ggtgtacacc cgccacgaga tcaaggacag cggcctgctg 2100

gactacacgg aggtccagcg ccgcaaccag ctgcacgacc tgcgcttcgc cgacatcgac 2160

acggtcatcc acgccgacgc caacgccgcc atgtttgcgg gcctgggcgc gttcttcgag 2220

gggatgggcg acctggggcg cgcggtcggc aaggtggtga tgggcatcgt gggcggcgtg 2280

gtatcggccg tgtcgggcgt gtcctccttc atgtccaacc cctttggggc gctggccgtg 2340

ggtctgttgg tcctggccgg cctggcggcg gccttcttcg cctttcgcta cgtcatgcgg 2400

ctgcagagca accccatgaa ggccctgtac ccgctaacca ccaaggagct caagaacccc 2460

accaacccgg acgcgtccgg ggagggcgag gagggcggcg actttgacga ggccaagcta 2520

gccgaggccc gggagatgat acggtacatg gccctggtgt ctgccatgga gcgcacggaa 2580

cacaaggcca agaagaaggg cacgagcgcg ctgctcagcg ccaaggtcac cgacatggtc 2640

atgcgcaagc gccgcaacac caactacacc caagttccca acaaagacgg tgacgccgac 2700

gaggacgacc tgtga 2715

<210> 62

<211> 2450

<212> DNA

<213> human herpesvirus 1 strain 17

<220>

<223> NC_001806.2:c46383-43867 human herpesvirus 1 strain

17, glycoprotein gH-UL22

<400> 62

atggggaatg gtttatggtt cgtgggggtt attattttgg gcgttgcgtg gggtcaggtc 60

cacgactgga ctgagcagac agacccatgg tttttggatg gcctgggcat ggaccgcatg 120

tactggcgcg acacgaacac cgggcgtctg tggctgccaa acacccccga cccccaaaaa 180

ccaccgcgcg gatttctggc gccgccggac gaactaaacc tgactacggc atctctgccc 240

cttcttcgct ggtacgagga gcgcttttgt tttgtattgg tcaccacggc cgagtttccg 300

cgggaccccg gccagctgct ttacatcccg aagacctacc tgctcggccg gcccccgaac 360

gcgagcctgc ccgcccccac cacggtcgag ccgaccgccc agcctccccc ctcggtcgcc 420

ccccttaagg gtctcttgca caatccagcc gcctccgtgt tgctgcgttc ccgggcctgg 480

gtaacgtttt cggccgtccc tgaccccgag gccctgacgt tcccgcgggg agacaacgtg 540

gcgacggcga gccacccgag cgggccgcgt gatacaccgc ccccccgacc gccggttggg 600

gcccggcggc acccgacgac ggagctggac atcacgcacc tgcacaacgc gtccacgacc 660

tggttggcca cccggggcct gttgagatcc ccaggtaggt acgtgtattt ctccccgtcg 720

gcctcgacgt ggcccgtggg catctggacg acgggggagc tggtgctcgg gtgcgatgcc 780

gcgctggtgc gcgcgcgcta cgggcgggaa ttcatggggc tcgtgatatc catgcacgac 840

agccctccgg tggaagtgat ggtggtcccc gcgggccaga cgctagatcg ggtcggggac 900

cccgcggacg aaaacccccc gggggctctt cccgggcccc cgggcggccc ccggtatcgg 960

gtctttgtcc tagggtccct gacgcgggcc gacaacggct ccgcgctgga cgccctccgc 1020

cgcgtgggcg gctacccgga ggagggcacg aactacgccc agttcctgtc gcgggcatac 1080

gcggagtttt tctcggggga cgcgggcgcc gagcagggcc cgcgcccccc tctcttctgg 1140

cgcctaacgg ggctgctcgc gacgtcgggt tttgctttcg tgaacgccgc ccacgcaaac 1200

ggcgcggtct gcctctccga cctgctaggc tttttggccc actcgcgcgc gcttgccggg 1260

ttggccgccc gcggggccgc gggctgtgcc gcggattctg tgttttttaa tgtgtcagtc 1320

ttggatccca cggcccgcct gcagctagag gctcggctcc agcacctggt ggccgagatt 1380

ctggagcgcg aacagagctt ggcattacac gcgctgggct atcagctggc cttcgtgctg 1440

gatagcccct cggcgtacga cgcagtggcg cccagcgcag cccatctcat cgacgccctg 1500

tatgccgagt ttctaggggg ccgcgtgctg accaccccgg tcgtccaccg ggcgctattt 1560

tacgcctcgg ctgtcctccg gcagccgttc ttggctggcg tcccctcggc ggtgcagcgg 1620

gaacgcgccc gccggagcct tctgatagcc tcggccctgt gtacgtccga cgtcgccgca 1680

gcgaccaacg ccgacctccg gaccgcgctg gcccgggccg accaccagaa aaccctcttt 1740

tggcttccgg accacttttc gccatgcgcg gcctccctgc gctttgatct agacgagagc 1800

gtgtttatcc tggacgcgct ggctcaagcc acccgatccg agaccccggt cgaagtcctg 1860

gcccagcaga cccacggcct cgcctcgacc ctgacgcgtt gggcacacta caacgccctg 1920

atccgcgcct tcgtccctga ggcctcacat cggtgcgggg ggcagtctgc caacgtcgag 1980

ccacggatcc tggtacccat cacccacaac gccagctacg tcgtcaccca ctcccctctg 2040

ccccggggga tcggctacaa gctcaccggc gtcgacgtcc gacgcccact gttcctaacc 2100

tacctcaccg cgacatgcga aggctccacc cgggatatcg agtccaagcg gctggtgcgc 2160

acccaaaacc agcgcgacct ggggctcgtg ggggccgtgt ttatgcgcta caccccggcc 2220

ggggaggtca tgtctgtgtt gctggtggat acggacaaca cacagcagca aatcgccgcc 2280

gggccgacgg agggcgcccc aagcgtgttt tcgagcgacg tgccgtccac ggccttgttg 2340

ctatttccaa acggaaccgt cattcatttg ctagcctttg acacgcagcc cgtggccgca 2400

attgcgcccg ggtttctggc cgcctctgcg ctgggcgtgg ttatgattac 2450

<210> 63

<211> 1185

<212> DNA

<213> artificial sequence

<220>

<223> SNP based on Rid1, human herpesvirus at gD NC_001806.2:138423-139607

1 strain 17, glycoprotein gD-US6 Gln52Pro (mature Gln 27) A155C

<400> 63

atgggggggg ctgccgccag gttgggggcc gtgattttgt ttgtcgtcat agtgggcctc 60

catggggtcc gcggcaaata tgccttggtg gatgcctctc tcaagatggc cgaccccaat 120

cgctttcgcg gcaaagacct tccggtcctg gacccgctga ccgaccctcc gggggtccgg 180

cgcgtgtacc acatccaggc gggcctaccg gacccgttcc agccccccag cctcccgatc 240

acggtttact acgccgtgtt ggagcgcgcc tgccgcagcg tgctcctaaa cgcaccgtcg 300

gaggcccccc agattgtccg cggggcctcc gaagacgtcc ggaaacaacc ctacaacctg 360

accatcgctt ggtttcggat gggaggcaac tgtgctatcc ccatcacggt catggagtac 420

accgaatgct cctacaacaa gtctctgggg gcctgtccca tccgaacgca gccccgctgg 480

aactactatg acagcttcag cgccgtcagc gaggataacc tggggttcct gatgcacgcc 540

cccgcgtttg agaccgccgg cacgtacctg cggctcgtga agataaacga ctggacggag 600

attacacagt ttatcctgga gcaccgagcc aagggctcct gtaagtacgc cctcccgctg 660

cgcatccccc cgtcagcctg cctctccccc caggcctacc agcagggggt gacggtggac 720

agcatcggga tgctgccccg cttcatcccc gagaaccagc gcaccgtcgc cgtatacagc 780

ttgaagatcg ccgggtggca cgggcccaag gccccataca cgagcaccct gctgcccccg 840

gagctgtccg agacccccaa cgccacgcag ccagaactcg ccccggaaga ccccgaggat 900

tcggccctct tggaggaccc cgtggggacg gtggcgccgc aaatcccacc aaactggcac 960

ataccgtcga tccaggacgc cgcgacgcct taccatcccc cggccacccc gaacaacatg 1020

ggcctgatcg ccggcgcggt gggcggcagt ctcctggcag ccctggtcat ttgcggaatt 1080

gtgtactgga tgcgccgcca cactcaaaaa gccccaaagc gcatacgcct cccccacatc 1140

cgggaagacg accagccgtc ctcgcaccag cccttgtttt actag 1185

<210> 64

<211> 394

<212> PRT

<213> artificial sequence

<220>

<223> amino acid sequence of sequence ID 63 encoded by SNP based on Rid1, having

Gln52Pro

<400> 64

Met Gly Gly Ala Ala Ala Arg Leu Gly Ala Val Ile Leu Phe Val Val

1 5 10 15

Ile Val Gly Leu His Gly Val Arg Gly Lys Tyr Ala Leu Val Asp Ala

20 25 30

Ser Leu Lys Met Ala Asp Pro Asn Arg Phe Arg Gly Lys Asp Leu Pro

35 40 45

Val Leu Asp Pro Leu Thr Asp Pro Pro Gly Val Arg Arg Val Tyr His

50 55 60

Ile Gln Ala Gly Leu Pro Asp Pro Phe Gln Pro Pro Ser Leu Pro Ile

65 70 75 80

Thr Val Tyr Tyr Ala Val Leu Glu Arg Ala Cys Arg Ser Val Leu Leu

85 90 95

Asn Ala Pro Ser Glu Ala Pro Gln Ile Val Arg Gly Ala Ser Glu Asp

100 105 110

Val Arg Lys Gln Pro Tyr Asn Leu Thr Ile Ala Trp Phe Arg Met Gly

115 120 125

Gly Asn Cys Ala Ile Pro Ile Thr Val Met Glu Tyr Thr Glu Cys Ser

130 135 140

Tyr Asn Lys Ser Leu Gly Ala Cys Pro Ile Arg Thr Gln Pro Arg Trp

145 150 155 160

Asn Tyr Tyr Asp Ser Phe Ser Ala Val Ser Glu Asp Asn Leu Gly Phe

165 170 175

Leu Met His Ala Pro Ala Phe Glu Thr Ala Gly Thr Tyr Leu Arg Leu

180 185 190

Val Lys Ile Asn Asp Trp Thr Glu Ile Thr Gln Phe Ile Leu Glu His

195 200 205

Arg Ala Lys Gly Ser Cys Lys Tyr Ala Leu Pro Leu Arg Ile Pro Pro

210 215 220

Ser Ala Cys Leu Ser Pro Gln Ala Tyr Gln Gln Gly Val Thr Val Asp

225 230 235 240

Ser Ile Gly Met Leu Pro Arg Phe Ile Pro Glu Asn Gln Arg Thr Val

245 250 255

Ala Val Tyr Ser Leu Lys Ile Ala Gly Trp His Gly Pro Lys Ala Pro

260 265 270

Tyr Thr Ser Thr Leu Leu Pro Pro Glu Leu Ser Glu Thr Pro Asn Ala

275 280 285

Thr Gln Pro Glu Leu Ala Pro Glu Asp Pro Glu Asp Ser Ala Leu Leu

290 295 300

Glu Asp Pro Val Gly Thr Val Ala Pro Gln Ile Pro Pro Asn Trp His

305 310 315 320

Ile Pro Ser Ile Gln Asp Ala Ala Thr Pro Tyr His Pro Pro Ala Thr

325 330 335

Pro Asn Asn Met Gly Leu Ile Ala Gly Ala Val Gly Gly Ser Leu Leu

340 345 350

Ala Ala Leu Val Ile Cys Gly Ile Val Tyr Trp Met Arg Arg His Thr

355 360 365

Gln Lys Ala Pro Lys Arg Ile Arg Leu Pro His Ile Arg Glu Asp Asp

370 375 380

Gln Pro Ser Ser His Gln Pro Leu Phe Tyr

385 390

<210> 65

<211> 1182

<212> DNA

<213> artificial sequence

<220>

<223> SNP based on Rid 1 in NC_001798.2:141016-142197 in human herpesvirus 2 strain HG52,

glycoprotein D-US 6A 155C

<400> 65

atggggcgtt tgacctccgg cgtcgggacg gcggccctgc tagttgtcgc ggtgggactc 60

cgcgtcgtct gcgccaaata cgccttagca gacccctcgc ttaagatggc cgatcccaat 120

cgatttcgcg ggaagaacct tccggttttg gacccgctga ccgacccccc cggggtgaag 180

cgtgtttacc acattcagcc gagcctggag gacccgttcc agccccccag catcccgatc 240

actgtgtact acgcagtgct ggaacgtgcc tgccgcagcg tgctcctaca tgccccatcg 300

gaggcccccc agatcgtgcg cggggcttcg gacgaggccc gaaagcacac gtacaacctg 360

accatcgcct ggtatcgcat gggagacaat tgcgctatcc ccatcacggt tatggaatac 420

accgagtgcc cctacaacaa gtcgttgggg gtctgcccca tccgaacgca gccccgctgg 480

agctactatg acagctttag cgccgtcagc gaggataacc tgggattcct gatgcacgcc 540

cccgccttcg agaccgcggg tacgtacctg cggctagtga agataaacga ctggacggag 600

atcacacaat ttatcctgga gcaccgggcc cgcgcctcct gcaagtacgc tctccccctg 660

cgcatccccc cggcagcgtg cctcacctcg aaggcctacc aacagggcgt gacggtcgac 720

agcatcggga tgctaccccg ctttatcccc gaaaaccagc gcaccgtcgc cctatacagc 780

ttaaaaatcg ccgggtggca cggccccaag cccccgtaca ccagcaccct gctgccgccg 840

gagctgtccg acaccaccaa cgccacgcaa cccgaactcg ttccggaaga ccccgaggac 900

tcggccctct tagaggatcc cgccgggacg gtgtcttcgc agatcccccc aaactggcac 960

atcccgtcga tccaggacgt cgcgccgcac cacgcccccg ccgcccccag caacccgggc 1020

ctgatcatcg gcgcgctggc cggcagtacc ctggcggtgc tggtcatcgg cggtattgcg 1080

ttttgggtac gccgccgcgc tcagatggcc cccaagcgcc tacgtctccc ccacatccgg 1140

gatgacgacg cgcccccctc gcaccagcca ttgttttact ag 1182

<210> 66

<211> 393

<212> PRT

<213> artificial sequence

<220>

<223> amino acid sequence of sequence ID 65 encoded by SNP based on Rid 1

Gln52Pro

<400> 66

Met Gly Arg Leu Thr Ser Gly Val Gly Thr Ala Ala Leu Leu Val Val

1 5 10 15

Ala Val Gly Leu Arg Val Val Cys Ala Lys Tyr Ala Leu Ala Asp Pro

20 25 30

Ser Leu Lys Met Ala Asp Pro Asn Arg Phe Arg Gly Lys Asn Leu Pro

35 40 45

Val Leu Asp Pro Leu Thr Asp Pro Pro Gly Val Lys Arg Val Tyr His

50 55 60

Ile Gln Pro Ser Leu Glu Asp Pro Phe Gln Pro Pro Ser Ile Pro Ile

65 70 75 80

Thr Val Tyr Tyr Ala Val Leu Glu Arg Ala Cys Arg Ser Val Leu Leu

85 90 95

His Ala Pro Ser Glu Ala Pro Gln Ile Val Arg Gly Ala Ser Asp Glu

100 105 110

Ala Arg Lys His Thr Tyr Asn Leu Thr Ile Ala Trp Tyr Arg Met Gly

115 120 125

Asp Asn Cys Ala Ile Pro Ile Thr Val Met Glu Tyr Thr Glu Cys Pro

130 135 140

Tyr Asn Lys Ser Leu Gly Val Cys Pro Ile Arg Thr Gln Pro Arg Trp

145 150 155 160

Ser Tyr Tyr Asp Ser Phe Ser Ala Val Ser Glu Asp Asn Leu Gly Phe

165 170 175

Leu Met His Ala Pro Ala Phe Glu Thr Ala Gly Thr Tyr Leu Arg Leu

180 185 190

Val Lys Ile Asn Asp Trp Thr Glu Ile Thr Gln Phe Ile Leu Glu His

195 200 205

Arg Ala Arg Ala Ser Cys Lys Tyr Ala Leu Pro Leu Arg Ile Pro Pro

210 215 220

Ala Ala Cys Leu Thr Ser Lys Ala Tyr Gln Gln Gly Val Thr Val Asp

225 230 235 240

Ser Ile Gly Met Leu Pro Arg Phe Ile Pro Glu Asn Gln Arg Thr Val

245 250 255

Ala Leu Tyr Ser Leu Lys Ile Ala Gly Trp His Gly Pro Lys Pro Pro

260 265 270

Tyr Thr Ser Thr Leu Leu Pro Pro Glu Leu Ser Asp Thr Thr Asn Ala

275 280 285

Thr Gln Pro Glu Leu Val Pro Glu Asp Pro Glu Asp Ser Ala Leu Leu

290 295 300

Glu Asp Pro Ala Gly Thr Val Ser Ser Gln Ile Pro Pro Asn Trp His

305 310 315 320

Ile Pro Ser Ile Gln Asp Val Ala Pro His His Ala Pro Ala Ala Pro

325 330 335

Ser Asn Pro Gly Leu Ile Ile Gly Ala Leu Ala Gly Ser Thr Leu Ala

340 345 350

Val Leu Val Ile Gly Gly Ile Ala Phe Trp Val Arg Arg Arg Ala Gln

355 360 365

Met Ala Pro Lys Arg Leu Arg Leu Pro His Ile Arg Asp Asp Asp Ala

370 375 380

Pro Pro Ser His Gln Pro Leu Phe Tyr

385 390

<210> 67

<211> 2715

<212> DNA

<213> artificial sequence

<220>

<223> beta 23 sheet double amino acid SNP at > NC_001806.2:c55795-53081

Human herpesvirus 1 strain 17, glycoprotein gB-UL 27Q 584A N585A

1750 CA-GC 1753 AA-GC

<400> 67

atgcgccagg gcgcccccgc gcgggggcgc cggtggttcg tcgtatgggc gctcttgggg 60

ttgacgctgg gggtcctggt ggcgtcggcg gctccgagtt cccccggcac gcctggggtc 120

gcggccgcga cccaggcggc gaacgggggc cctgccactc cggcgccgcc cgcccctggc 180

gcccccccaa cgggggaccc gaaaccgaag aagaacaaaa aaccgaaacc cccaaagccg 240

ccgcgccccg ccggcgacaa cgcgaccgtc gccgcgggcc acgccaccct gcgcgagcac 300

ctgcgggaca tcaaggcgga gaacaccgat gcaaactttt acgtgtgccc accccccacg 360

ggcgccacgg tggtgcagtt cgagcagccg cgccgctgcc cgacccggcc cgagggtcag 420

aactacacgg agggcatcgc ggtggtcttc aaggagaaca tcgccccgta caagttcaag 480

gccaccatgt actacaaaga cgtcaccgtt tcgcaggtgt ggttcggcca ccgctactcc 540

cagtttatgg ggatctttga ggaccgcgcc cccgtcccct tcgaggaggt gatcgacaag 600

atcaacgcca agggggtctg tcggtccacg gccaagtacg tgcgcaacaa cctggagacc 660

accgcgtttc accgggacga ccacgagacc gacatggagc tgaaaccggc caacgccgcg 720

acccgcacga gccggggctg gcacaccacc gacctcaagt acaacccctc gcgggtggag 780

gcgttccacc ggtacgggac gacggtaaac tgcatcgtcg aggaggtgga cgcgcgctcg 840

gtgtacccgt acgacgagtt tgtgttggcg actggcgact ttgtgtacat gtccccgttt 900

tacggctacc gggaggggtc gcacaccgaa cacaccagct acgccgccga ccgcttcaag 960

caggtcgacg gcttctacgc gcgcgacctc accaccaagg cccgggccac ggcgccgacc 1020

acccggaacc tgctcacgac ccccaagttc accgtggcct gggactgggt gccaaagcgc 1080

ccgtcggtct gcaccatgac caagtggcag gaggtggacg agatgctgcg ctccgagtac 1140

ggcggctcct tccgattctc ttccgacgcc atatccacca ccttcaccac caacctgacc 1200

gagtacccgc tctcgcgcgt ggacctgggg gactgcatcg gcaaggacgc ccgcgacgcc 1260

atggaccgca tcttcgcccg caggtacaac gcgacgcaca tcaaggtggg ccagccgcag 1320

tactacctgg ccaatggggg ctttctgatc gcgtaccagc cccttctcag caacacgctc 1380

gcggagctgt acgtgcggga acacctccgc gagcagagcc gcaagccccc aaaccccacg 1440

cccccgccgc ccggggccag cgccaacgcg tccgtggagc gcatcaagac cacctcctcc 1500

atcgagttcg ccaggctgca gtttacgtac aaccacatac agcgccatgt caacgatatg 1560

ttgggccgcg ttgccatcgc gtggtgcgag ctgcagaatc acgagctgac cctgtggaac 1620

gaggcccgca agctgaaccc caacgccatc gcctcggcca ccgtgggccg gcgggtgagc 1680

gcgcggatgc tcggcgacgt gatggccgtc tccacgtgcg tgccggtcgc cgcggacaac 1740

gtgatcgtcg cagcctcgat gcgcatcagc tcgcggcccg gggcctgcta cagccgcccc 1800

ctggtcagct ttcggtacga agaccagggc ccgttggtcg aggggcagct gggggagaac 1860

aacgagctgc ggctgacgcg cgatgcgatc gagccgtgca ccgtgggaca ccggcgctac 1920

ttcaccttcg gtgggggcta cgtgtacttc gaggagtacg cgtactccca ccagctgagc 1980

cgcgccgaca tcaccaccgt cagcaccttc atcgacctca acatcaccat gctggaggat 2040

cacgagtttg tccccctgga ggtgtacacc cgccacgaga tcaaggacag cggcctgctg 2100

gactacacgg aggtccagcg ccgcaaccag ctgcacgacc tgcgcttcgc cgacatcgac 2160

acggtcatcc acgccgacgc caacgccgcc atgtttgcgg gcctgggcgc gttcttcgag 2220

gggatgggcg acctggggcg cgcggtcggc aaggtggtga tgggcatcgt gggcggcgtg 2280

gtatcggccg tgtcgggcgt gtcctccttc atgtccaacc cctttggggc gctggccgtg 2340

ggtctgttgg tcctggccgg cctggcggcg gccttcttcg cctttcgcta cgtcatgcgg 2400

ctgcagagca accccatgaa ggccctgtac ccgctaacca ccaaggagct caagaacccc 2460

accaacccgg acgcgtccgg ggagggcgag gagggcggcg actttgacga ggccaagcta 2520

gccgaggccc gggagatgat acggtacatg gccctggtgt ctgccatgga gcgcacggaa 2580

cacaaggcca agaagaaggg cacgagcgcg ctgctcagcg ccaaggtcac cgacatggtc 2640

atgcgcaagc gccgcaacac caactacacc caagttccca acaaagacgg tgacgccgac 2700

gaggacgacc tgtga 2715

<210> 68

<211> 2715

<212> DNA

<213> artificial sequence

<220>

<223> beta 23 sheet single amino acid SNP in

Nc_001806.2:c55795-53081 human herpesvirus 1 strain

17, glycoprotein gB-UL 27Q 584A N A1750 CA-GC 1753 AA-GC

<400> 68

atgcgccagg gcgcccccgc gcgggggcgc cggtggttcg tcgtatgggc gctcttgggg 60

ttgacgctgg gggtcctggt ggcgtcggcg gctccgagtt cccccggcac gcctggggtc 120

gcggccgcga cccaggcggc gaacgggggc cctgccactc cggcgccgcc cgcccctggc 180

gcccccccaa cgggggaccc gaaaccgaag aagaacaaaa aaccgaaacc cccaaagccg 240

ccgcgccccg ccggcgacaa cgcgaccgtc gccgcgggcc acgccaccct gcgcgagcac 300

ctgcgggaca tcaaggcgga gaacaccgat gcaaactttt acgtgtgccc accccccacg 360

ggcgccacgg tggtgcagtt cgagcagccg cgccgctgcc cgacccggcc cgagggtcag 420

aactacacgg agggcatcgc ggtggtcttc aaggagaaca tcgccccgta caagttcaag 480

gccaccatgt actacaaaga cgtcaccgtt tcgcaggtgt ggttcggcca ccgctactcc 540

cagtttatgg ggatctttga ggaccgcgcc cccgtcccct tcgaggaggt gatcgacaag 600

atcaacgcca agggggtctg tcggtccacg gccaagtacg tgcgcaacaa cctggagacc 660

accgcgtttc accgggacga ccacgagacc gacatggagc tgaaaccggc caacgccgcg 720

acccgcacga gccggggctg gcacaccacc gacctcaagt acaacccctc gcgggtggag 780

gcgttccacc ggtacgggac gacggtaaac tgcatcgtcg aggaggtgga cgcgcgctcg 840

gtgtacccgt acgacgagtt tgtgttggcg actggcgact ttgtgtacat gtccccgttt 900

tacggctacc gggaggggtc gcacaccgaa cacaccagct acgccgccga ccgcttcaag 960

caggtcgacg gcttctacgc gcgcgacctc accaccaagg cccgggccac ggcgccgacc 1020

acccggaacc tgctcacgac ccccaagttc accgtggcct gggactgggt gccaaagcgc 1080

ccgtcggtct gcaccatgac caagtggcag gaggtggacg agatgctgcg ctccgagtac 1140

ggcggctcct tccgattctc ttccgacgcc atatccacca ccttcaccac caacctgacc 1200

gagtacccgc tctcgcgcgt ggacctgggg gactgcatcg gcaaggacgc ccgcgacgcc 1260

atggaccgca tcttcgcccg caggtacaac gcgacgcaca tcaaggtggg ccagccgcag 1320

tactacctgg ccaatggggg ctttctgatc gcgtaccagc cccttctcag caacacgctc 1380

gcggagctgt acgtgcggga acacctccgc gagcagagcc gcaagccccc aaaccccacg 1440

cccccgccgc ccggggccag cgccaacgcg tccgtggagc gcatcaagac cacctcctcc 1500

atcgagttcg ccaggctgca gtttacgtac aaccacatac agcgccatgt caacgatatg 1560

ttgggccgcg ttgccatcgc gtggtgcgag ctgcagaatc acgagctgac cctgtggaac 1620

gaggcccgca agctgaaccc caacgccatc gcctcggcca ccgtgggccg gcgggtgagc 1680

gcgcggatgc tcggcgacgt gatggccgtc tccacgtgcg tgccggtcgc cgcggacaac 1740

gtgatcgtcc aagcctcgat gcgcatcagc tcgcggcccg gggcctgcta cagccgcccc 1800

ctggtcagct ttcggtacga agaccagggc ccgttggtcg aggggcagct gggggagaac 1860

aacgagctgc ggctgacgcg cgatgcgatc gagccgtgca ccgtgggaca ccggcgctac 1920

ttcaccttcg gtgggggcta cgtgtacttc gaggagtacg cgtactccca ccagctgagc 1980

cgcgccgaca tcaccaccgt cagcaccttc atcgacctca acatcaccat gctggaggat 2040

cacgagtttg tccccctgga ggtgtacacc cgccacgaga tcaaggacag cggcctgctg 2100

gactacacgg aggtccagcg ccgcaaccag ctgcacgacc tgcgcttcgc cgacatcgac 2160

acggtcatcc acgccgacgc caacgccgcc atgtttgcgg gcctgggcgc gttcttcgag 2220

gggatgggcg acctggggcg cgcggtcggc aaggtggtga tgggcatcgt gggcggcgtg 2280

gtatcggccg tgtcgggcgt gtcctccttc atgtccaacc cctttggggc gctggccgtg 2340

ggtctgttgg tcctggccgg cctggcggcg gccttcttcg cctttcgcta cgtcatgcgg 2400

ctgcagagca accccatgaa ggccctgtac ccgctaacca ccaaggagct caagaacccc 2460

accaacccgg acgcgtccgg ggagggcgag gagggcggcg actttgacga ggccaagcta 2520

gccgaggccc gggagatgat acggtacatg gccctggtgt ctgccatgga gcgcacggaa 2580

cacaaggcca agaagaaggg cacgagcgcg ctgctcagcg ccaaggtcac cgacatggtc 2640

atgcgcaagc gccgcaacac caactacacc caagttccca acaaagacgg tgacgccgac 2700

gaggacgacc tgtga 2715

<210> 69

<211> 2715

<212> DNA

<213> artificial sequence

<220>

<223> beta 30 sheet double amino acid SNP, in > NC_001806.2:c55795-53081

On human herpesvirus 1 strain 17, glycoprotein gB-UL 27Y 555A Q558A

1963TA-GC 1972-TA-GC

<400> 69

atgcgccagg gcgcccccgc gcgggggcgc cggtggttcg tcgtatgggc gctcttgggg 60

ttgacgctgg gggtcctggt ggcgtcggcg gctccgagtt cccccggcac gcctggggtc 120

gcggccgcga cccaggcggc gaacgggggc cctgccactc cggcgccgcc cgcccctggc 180

gcccccccaa cgggggaccc gaaaccgaag aagaacaaaa aaccgaaacc cccaaagccg 240

ccgcgccccg ccggcgacaa cgcgaccgtc gccgcgggcc acgccaccct gcgcgagcac 300

ctgcgggaca tcaaggcgga gaacaccgat gcaaactttt acgtgtgccc accccccacg 360

ggcgccacgg tggtgcagtt cgagcagccg cgccgctgcc cgacccggcc cgagggtcag 420

aactacacgg agggcatcgc ggtggtcttc aaggagaaca tcgccccgta caagttcaag 480

gccaccatgt actacaaaga cgtcaccgtt tcgcaggtgt ggttcggcca ccgctactcc 540

cagtttatgg ggatctttga ggaccgcgcc cccgtcccct tcgaggaggt gatcgacaag 600

atcaacgcca agggggtctg tcggtccacg gccaagtacg tgcgcaacaa cctggagacc 660

accgcgtttc accgggacga ccacgagacc gacatggagc tgaaaccggc caacgccgcg 720

acccgcacga gccggggctg gcacaccacc gacctcaagt acaacccctc gcgggtggag 780

gcgttccacc ggtacgggac gacggtaaac tgcatcgtcg aggaggtgga cgcgcgctcg 840

gtgtacccgt acgacgagtt tgtgttggcg actggcgact ttgtgtacat gtccccgttt 900

tacggctacc gggaggggtc gcacaccgaa cacaccagct acgccgccga ccgcttcaag 960

caggtcgacg gcttctacgc gcgcgacctc accaccaagg cccgggccac ggcgccgacc 1020

acccggaacc tgctcacgac ccccaagttc accgtggcct gggactgggt gccaaagcgc 1080

ccgtcggtct gcaccatgac caagtggcag gaggtggacg agatgctgcg ctccgagtac 1140

ggcggctcct tccgattctc ttccgacgcc atatccacca ccttcaccac caacctgacc 1200

gagtacccgc tctcgcgcgt ggacctgggg gactgcatcg gcaaggacgc ccgcgacgcc 1260

atggaccgca tcttcgcccg caggtacaac gcgacgcaca tcaaggtggg ccagccgcag 1320

tactacctgg ccaatggggg ctttctgatc gcgtaccagc cccttctcag caacacgctc 1380

gcggagctgt acgtgcggga acacctccgc gagcagagcc gcaagccccc aaaccccacg 1440

cccccgccgc ccggggccag cgccaacgcg tccgtggagc gcatcaagac cacctcctcc 1500

atcgagttcg ccaggctgca gtttacgtac aaccacatac agcgccatgt caacgatatg 1560

ttgggccgcg ttgccatcgc gtggtgcgag ctgcagaatc acgagctgac cctgtggaac 1620

gaggcccgca agctgaaccc caacgccatc gcctcggcca ccgtgggccg gcgggtgagc 1680

gcgcggatgc tcggcgacgt gatggccgtc tccacgtgcg tgccggtcgc cgcggacaac 1740

gtgatcgtcc aaaactcgat gcgcatcagc tcgcggcccg gggcctgcta cagccgcccc 1800

ctggtcagct ttcggtacga agaccagggc ccgttggtcg aggggcagct gggggagaac 1860

aacgagctgc ggctgacgcg cgatgcgatc gagccgtgca ccgtgggaca ccggcgctac 1920

ttcaccttcg gtgggggcta cgtgtacttc gaggagtacg cggcctccca cgcgctgagc 1980

cgcgccgaca tcaccaccgt cagcaccttc atcgacctca acatcaccat gctggaggat 2040

cacgagtttg tccccctgga ggtgtacacc cgccacgaga tcaaggacag cggcctgctg 2100

gactacacgg aggtccagcg ccgcaaccag ctgcacgacc tgcgcttcgc cgacatcgac 2160

acggtcatcc acgccgacgc caacgccgcc atgtttgcgg gcctgggcgc gttcttcgag 2220

gggatgggcg acctggggcg cgcggtcggc aaggtggtga tgggcatcgt gggcggcgtg 2280

gtatcggccg tgtcgggcgt gtcctccttc atgtccaacc cctttggggc gctggccgtg 2340

ggtctgttgg tcctggccgg cctggcggcg gccttcttcg cctttcgcta cgtcatgcgg 2400

ctgcagagca accccatgaa ggccctgtac ccgctaacca ccaaggagct caagaacccc 2460

accaacccgg acgcgtccgg ggagggcgag gagggcggcg actttgacga ggccaagcta 2520

gccgaggccc gggagatgat acggtacatg gccctggtgt ctgccatgga gcgcacggaa 2580

cacaaggcca agaagaaggg cacgagcgcg ctgctcagcg ccaaggtcac cgacatggtc 2640

atgcgcaagc gccgcaacac caactacacc caagttccca acaaagacgg tgacgccgac 2700

gaggacgacc tgtga 2715

<210> 70

<211> 2715

<212> DNA

<213> artificial sequence

<220>

<223> beta 30 sheet single amino acid SNP, at > NC_001806.2:c55795-53081

On human herpesvirus 1 strain 17, glycoprotein gB-UL 27Q 558A

1972-TA-GC

<400> 70

atgcgccagg gcgcccccgc gcgggggcgc cggtggttcg tcgtatgggc gctcttgggg 60

ttgacgctgg gggtcctggt ggcgtcggcg gctccgagtt cccccggcac gcctggggtc 120

gcggccgcga cccaggcggc gaacgggggc cctgccactc cggcgccgcc cgcccctggc 180

gcccccccaa cgggggaccc gaaaccgaag aagaacaaaa aaccgaaacc cccaaagccg 240

ccgcgccccg ccggcgacaa cgcgaccgtc gccgcgggcc acgccaccct gcgcgagcac 300

ctgcgggaca tcaaggcgga gaacaccgat gcaaactttt acgtgtgccc accccccacg 360

ggcgccacgg tggtgcagtt cgagcagccg cgccgctgcc cgacccggcc cgagggtcag 420

aactacacgg agggcatcgc ggtggtcttc aaggagaaca tcgccccgta caagttcaag 480

gccaccatgt actacaaaga cgtcaccgtt tcgcaggtgt ggttcggcca ccgctactcc 540

cagtttatgg ggatctttga ggaccgcgcc cccgtcccct tcgaggaggt gatcgacaag 600

atcaacgcca agggggtctg tcggtccacg gccaagtacg tgcgcaacaa cctggagacc 660

accgcgtttc accgggacga ccacgagacc gacatggagc tgaaaccggc caacgccgcg 720

acccgcacga gccggggctg gcacaccacc gacctcaagt acaacccctc gcgggtggag 780

gcgttccacc ggtacgggac gacggtaaac tgcatcgtcg aggaggtgga cgcgcgctcg 840

gtgtacccgt acgacgagtt tgtgttggcg actggcgact ttgtgtacat gtccccgttt 900

tacggctacc gggaggggtc gcacaccgaa cacaccagct acgccgccga ccgcttcaag 960

caggtcgacg gcttctacgc gcgcgacctc accaccaagg cccgggccac ggcgccgacc 1020

acccggaacc tgctcacgac ccccaagttc accgtggcct gggactgggt gccaaagcgc 1080

ccgtcggtct gcaccatgac caagtggcag gaggtggacg agatgctgcg ctccgagtac 1140

ggcggctcct tccgattctc ttccgacgcc atatccacca ccttcaccac caacctgacc 1200

gagtacccgc tctcgcgcgt ggacctgggg gactgcatcg gcaaggacgc ccgcgacgcc 1260

atggaccgca tcttcgcccg caggtacaac gcgacgcaca tcaaggtggg ccagccgcag 1320

tactacctgg ccaatggggg ctttctgatc gcgtaccagc cccttctcag caacacgctc 1380

gcggagctgt acgtgcggga acacctccgc gagcagagcc gcaagccccc aaaccccacg 1440

cccccgccgc ccggggccag cgccaacgcg tccgtggagc gcatcaagac cacctcctcc 1500

atcgagttcg ccaggctgca gtttacgtac aaccacatac agcgccatgt caacgatatg 1560

ttgggccgcg ttgccatcgc gtggtgcgag ctgcagaatc acgagctgac cctgtggaac 1620

gaggcccgca agctgaaccc caacgccatc gcctcggcca ccgtgggccg gcgggtgagc 1680

gcgcggatgc tcggcgacgt gatggccgtc tccacgtgcg tgccggtcgc cgcggacaac 1740

gtgatcgtcc aaaactcgat gcgcatcagc tcgcggcccg gggcctgcta cagccgcccc 1800

ctggtcagct ttcggtacga agaccagggc ccgttggtcg aggggcagct gggggagaac 1860

aacgagctgc ggctgacgcg cgatgcgatc gagccgtgca ccgtgggaca ccggcgctac 1920

ttcaccttcg gtgggggcta cgtgtacttc gaggagtacg cgtactccca cgcgctgagc 1980

cgcgccgaca tcaccaccgt cagcaccttc atcgacctca acatcaccat gctggaggat 2040

cacgagtttg tccccctgga ggtgtacacc cgccacgaga tcaaggacag cggcctgctg 2100

gactacacgg aggtccagcg ccgcaaccag ctgcacgacc tgcgcttcgc cgacatcgac 2160

acggtcatcc acgccgacgc caacgccgcc atgtttgcgg gcctgggcgc gttcttcgag 2220

gggatgggcg acctggggcg cgcggtcggc aaggtggtga tgggcatcgt gggcggcgtg 2280

gtatcggccg tgtcgggcgt gtcctccttc atgtccaacc cctttggggc gctggccgtg 2340

ggtctgttgg tcctggccgg cctggcggcg gccttcttcg cctttcgcta cgtcatgcgg 2400

ctgcagagca accccatgaa ggccctgtac ccgctaacca ccaaggagct caagaacccc 2460

accaacccgg acgcgtccgg ggagggcgag gagggcggcg actttgacga ggccaagcta 2520

gccgaggccc gggagatgat acggtacatg gccctggtgt ctgccatgga gcgcacggaa 2580

cacaaggcca agaagaaggg cacgagcgcg ctgctcagcg ccaaggtcac cgacatggtc 2640

atgcgcaagc gccgcaacac caactacacc caagttccca acaaagacgg tgacgccgac 2700

gaggacgacc tgtga 2715

<210> 71

<211> 2715

<212> DNA

<213> artificial sequence

<220>

<223> beta 23-sheet double amino acid SNPS, at NC_001798.2:c56152-53438

Human herpesvirus 2 strain HG52, glycoprotein B-UL27 1682 CA-GC

1685 AA-GC 581QN582 AA

<400> 71

atgcgcgggg ggggcttgat ttgcgcgctg gtcgtggggg cgctggtggc cgcggtggcg 60

tcggcggccc cggcggcccc ggcggccccc cgcgcctcgg gcggcgtggc cgcgaccgtc 120

gcggcgaacg ggggtcccgc ctcccggccg ccccccgtcc cgagccccgc gaccaccaag 180

gcccggaagc ggaaaaccaa aaagccgccc aagcggcccg aggcgacccc gccccccgac 240

gccaacgcga ccgtcgccgc cggccacgcc acgctgcgcg cgcacctgcg ggaaatcaag 300

gtcgagaacg ccgatgccca gttttacgtg tgcccgcccc cgacgggcgc cacggtggtg 360

cagtttgagc agccgcgccg ctgcccgacg cgcccggagg ggcagaacta cacggagggc 420

atcgcggtgg tcttcaagga gaacatcgcc ccgtacaaat tcaaggccac catgtactac 480

aaagacgtga ccgtgtcgca ggtgtggttc ggccaccgct actcccagtt tatggggata 540

ttcgaggacc gcgcccccgt tcccttcgag gaggtgatcg acaagattaa cgccaagggg 600

gtctgccgct ccacggccaa gtacgtgcgg aacaacatgg agaccaccgc gtttcaccgg 660

gacgaccacg agaccgacat ggagctcaag ccggcgaagg tcgccacgcg cacgagccgg 720

gggtggcaca ccaccgacct caagtacaac ccctcgcggg tggaggcgtt ccatcggtac 780

ggcacgacgg tcaactgcat cgtcgaggag gtggacgcgc ggtcggtgta cccgtacgat 840

gagtttgtgc tggcgacggg cgactttgtg tacatgtccc cgttttacgg ctaccgggag 900

gggtcgcaca ccgagcacac cagctacgcc gccgaccgct tcaagcaggt cgacggcttc 960

tacgcgcgcg acctcaccac gaaggcccgg gccacgtcgc cgacgacccg caacttgctg 1020

acgaccccca agtttaccgt ggcctgggac tgggtgccga agcgaccggc ggtctgcacc 1080

atgaccaagt ggcaggaggt ggacgagatg ctccgcgccg agtacggcgg ctccttccgc 1140

ttctcctccg acgccatctc gaccaccttc accaccaacc tgaccgagta ctcgctctcg 1200

cgcgtcgacc tgggcgactg catcggccgg gatgcccgcg aggccatcga ccgcatgttt 1260

gcgcgcaagt acaacgccac gcacatcaag gtgggccagc cgcagtacta cctggccacg 1320

gggggcttcc tcatcgcgta ccagcccctc ctcagcaaca cgctcgccga gctgtacgtg 1380

cgggagtaca tgcgggagca ggaccgcaag ccccggaatg ccacgcccgc gccactgcgg 1440

gaggcgccca gcgccaacgc gtccgtggag cgcatcaaga ccacctcctc gatcgagttc 1500

gcccggctgc agtttacgta taaccacata cagcgccacg tgaacgacat gctggggcgc 1560

atcgccgtcg cgtggtgcga gctgcagaac cacgagctga ctctctggaa cgaggcccgc 1620

aagctcaacc ccaacgccat cgcctccgcc accgtcggcc ggcgggtgag cgcgcgcatg 1680

ctcggagacg tcatggccgt ctccacgtgc gtgcccgtcg ccccggacaa cgtgatcgtg 1740

gcggcctcga tgcgcgtcag ctcgcggccg gggacgtgct acagccgccc cctggtcagc 1800

tttcggtacg aagaccaggg cccgctgatc gaggggcagc tgggcgagaa caacgagctg 1860

cgcctcaccc gcgacgcgct cgagccgtgc accgtgggcc accggcgcta cttcatcttc 1920

ggcgggggct acgtgtactt cgaggagtac gcgtactctc accagctgag tcgcgccgac 1980

gtcaccaccg tcagcacctt catcgacctg aacatcacca tgctggagga ccacgagttt 2040

gtgcccctgg aggtctacac gcgccacgag atcaaggaca gcggcctgct ggactacacg 2100

gaggtccagc gccgcaacca gctgcacgac ctgcgctttg ccgacatcga cacggtcatc 2160

cgcgccgacg ccaacgccgc catgttcgcg gggctgtgcg cgttcttcga ggggatgggg 2220

gacttggggc gcgcggtcgg caaggtagtc atgggagtag tggggggcgt ggtgtcggcc 2280

gtctcgggcg tgtcctcctt tatgtccaac cccttcgggg cgcttgccgt ggggctgctg 2340

gtcctggccg gcctggtcgc ggccttcttc gccttccgct acgtcctgca actgcaacgc 2400

aatcccatga aggccctgta tccgctcacc accaaggaac tcaagacttc cgaccccggg 2460

ggcgtgggcg gggaggggga ggaaggcgcg gaggggggcg ggtttgacga ggccaagttg 2520

gccgaggccc gagaaatgat ccgatatatg gctttggtgt cggccatgga gcgcacggaa 2580

cacaaggcca gaaagaaggg cacgagcgcc ctgctcagct ccaaggtcac caacatggtt 2640

ctgcgcaagc gcaacaaagc caggtactct ccgctccaca acgaggacga ggccggagac 2700

gaagacgagc tctaa 2715

<210> 72

<211> 2715

<212> DNA

<213> artificial sequence

<220>

<223> beta 23 sheet single amino acid SNP at NC_001798.2:c56152-53438

Human herpesvirus 2 strain HG52, glycoprotein B-UL27 1685 AA-GC

N582A

<400> 72

atgcgcgggg ggggcttgat ttgcgcgctg gtcgtggggg cgctggtggc cgcggtggcg 60

tcggcggccc cggcggcccc ggcggccccc cgcgcctcgg gcggcgtggc cgcgaccgtc 120

gcggcgaacg ggggtcccgc ctcccggccg ccccccgtcc cgagccccgc gaccaccaag 180

gcccggaagc ggaaaaccaa aaagccgccc aagcggcccg aggcgacccc gccccccgac 240

gccaacgcga ccgtcgccgc cggccacgcc acgctgcgcg cgcacctgcg ggaaatcaag 300

gtcgagaacg ccgatgccca gttttacgtg tgcccgcccc cgacgggcgc cacggtggtg 360

cagtttgagc agccgcgccg ctgcccgacg cgcccggagg ggcagaacta cacggagggc 420

atcgcggtgg tcttcaagga gaacatcgcc ccgtacaaat tcaaggccac catgtactac 480

aaagacgtga ccgtgtcgca ggtgtggttc ggccaccgct actcccagtt tatggggata 540

ttcgaggacc gcgcccccgt tcccttcgag gaggtgatcg acaagattaa cgccaagggg 600

gtctgccgct ccacggccaa gtacgtgcgg aacaacatgg agaccaccgc gtttcaccgg 660

gacgaccacg agaccgacat ggagctcaag ccggcgaagg tcgccacgcg cacgagccgg 720

gggtggcaca ccaccgacct caagtacaac ccctcgcggg tggaggcgtt ccatcggtac 780

ggcacgacgg tcaactgcat cgtcgaggag gtggacgcgc ggtcggtgta cccgtacgat 840

gagtttgtgc tggcgacggg cgactttgtg tacatgtccc cgttttacgg ctaccgggag 900

gggtcgcaca ccgagcacac cagctacgcc gccgaccgct tcaagcaggt cgacggcttc 960

tacgcgcgcg acctcaccac gaaggcccgg gccacgtcgc cgacgacccg caacttgctg 1020

acgaccccca agtttaccgt ggcctgggac tgggtgccga agcgaccggc ggtctgcacc 1080

atgaccaagt ggcaggaggt ggacgagatg ctccgcgccg agtacggcgg ctccttccgc 1140

ttctcctccg acgccatctc gaccaccttc accaccaacc tgaccgagta ctcgctctcg 1200

cgcgtcgacc tgggcgactg catcggccgg gatgcccgcg aggccatcga ccgcatgttt 1260

gcgcgcaagt acaacgccac gcacatcaag gtgggccagc cgcagtacta cctggccacg 1320

gggggcttcc tcatcgcgta ccagcccctc ctcagcaaca cgctcgccga gctgtacgtg 1380

cgggagtaca tgcgggagca ggaccgcaag ccccggaatg ccacgcccgc gccactgcgg 1440

gaggcgccca gcgccaacgc gtccgtggag cgcatcaaga ccacctcctc gatcgagttc 1500

gcccggctgc agtttacgta taaccacata cagcgccacg tgaacgacat gctggggcgc 1560

atcgccgtcg cgtggtgcga gctgcagaac cacgagctga ctctctggaa cgaggcccgc 1620

aagctcaacc ccaacgccat cgcctccgcc accgtcggcc ggcgggtgag cgcgcgcatg 1680

ctcggagacg tcatggccgt ctccacgtgc gtgcccgtcg ccccggacaa cgtgatcgtg 1740

caggcctcga tgcgcgtcag ctcgcggccg gggacgtgct acagccgccc cctggtcagc 1800

tttcggtacg aagaccaggg cccgctgatc gaggggcagc tgggcgagaa caacgagctg 1860

cgcctcaccc gcgacgcgct cgagccgtgc accgtgggcc accggcgcta cttcatcttc 1920

ggcgggggct acgtgtactt cgaggagtac gcgtactctc accagctgag tcgcgccgac 1980

gtcaccaccg tcagcacctt catcgacctg aacatcacca tgctggagga ccacgagttt 2040

gtgcccctgg aggtctacac gcgccacgag atcaaggaca gcggcctgct ggactacacg 2100

gaggtccagc gccgcaacca gctgcacgac ctgcgctttg ccgacatcga cacggtcatc 2160

cgcgccgacg ccaacgccgc catgttcgcg gggctgtgcg cgttcttcga ggggatgggg 2220

gacttggggc gcgcggtcgg caaggtagtc atgggagtag tggggggcgt ggtgtcggcc 2280

gtctcgggcg tgtcctcctt tatgtccaac cccttcgggg cgcttgccgt ggggctgctg 2340

gtcctggccg gcctggtcgc ggccttcttc gccttccgct acgtcctgca actgcaacgc 2400

aatcccatga aggccctgta tccgctcacc accaaggaac tcaagacttc cgaccccggg 2460

ggcgtgggcg gggaggggga ggaaggcgcg gaggggggcg ggtttgacga ggccaagttg 2520

gccgaggccc gagaaatgat ccgatatatg gctttggtgt cggccatgga gcgcacggaa 2580

cacaaggcca gaaagaaggg cacgagcgcc ctgctcagct ccaaggtcac caacatggtt 2640

ctgcgcaagc gcaacaaagc caggtactct ccgctccaca acgaggacga ggccggagac 2700

gaagacgagc tctaa 2715

<210> 73

<211> 2715

<212> DNA

<213> artificial sequence

<220>

<223> beta 30 sheet double amino acid SNP at NC_001798.2 c56152-53438

Human herpesvirus 2 strain HG52, glycoprotein B-UL 27Y 652A Q655A

1954TA-GC 1963CA-GC

<400> 73

atgcgcgggg ggggcttgat ttgcgcgctg gtcgtggggg cgctggtggc cgcggtggcg 60

tcggcggccc cggcggcccc ggcggccccc cgcgcctcgg gcggcgtggc cgcgaccgtc 120

gcggcgaacg ggggtcccgc ctcccggccg ccccccgtcc cgagccccgc gaccaccaag 180

gcccggaagc ggaaaaccaa aaagccgccc aagcggcccg aggcgacccc gccccccgac 240

gccaacgcga ccgtcgccgc cggccacgcc acgctgcgcg cgcacctgcg ggaaatcaag 300

gtcgagaacg ccgatgccca gttttacgtg tgcccgcccc cgacgggcgc cacggtggtg 360

cagtttgagc agccgcgccg ctgcccgacg cgcccggagg ggcagaacta cacggagggc 420

atcgcggtgg tcttcaagga gaacatcgcc ccgtacaaat tcaaggccac catgtactac 480

aaagacgtga ccgtgtcgca ggtgtggttc ggccaccgct actcccagtt tatggggata 540

ttcgaggacc gcgcccccgt tcccttcgag gaggtgatcg acaagattaa cgccaagggg 600

gtctgccgct ccacggccaa gtacgtgcgg aacaacatgg agaccaccgc gtttcaccgg 660

gacgaccacg agaccgacat ggagctcaag ccggcgaagg tcgccacgcg cacgagccgg 720

gggtggcaca ccaccgacct caagtacaac ccctcgcggg tggaggcgtt ccatcggtac 780

ggcacgacgg tcaactgcat cgtcgaggag gtggacgcgc ggtcggtgta cccgtacgat 840

gagtttgtgc tggcgacggg cgactttgtg tacatgtccc cgttttacgg ctaccgggag 900

gggtcgcaca ccgagcacac cagctacgcc gccgaccgct tcaagcaggt cgacggcttc 960

tacgcgcgcg acctcaccac gaaggcccgg gccacgtcgc cgacgacccg caacttgctg 1020

acgaccccca agtttaccgt ggcctgggac tgggtgccga agcgaccggc ggtctgcacc 1080

atgaccaagt ggcaggaggt ggacgagatg ctccgcgccg agtacggcgg ctccttccgc 1140

ttctcctccg acgccatctc gaccaccttc accaccaacc tgaccgagta ctcgctctcg 1200

cgcgtcgacc tgggcgactg catcggccgg gatgcccgcg aggccatcga ccgcatgttt 1260

gcgcgcaagt acaacgccac gcacatcaag gtgggccagc cgcagtacta cctggccacg 1320

gggggcttcc tcatcgcgta ccagcccctc ctcagcaaca cgctcgccga gctgtacgtg 1380

cgggagtaca tgcgggagca ggaccgcaag ccccggaatg ccacgcccgc gccactgcgg 1440

gaggcgccca gcgccaacgc gtccgtggag cgcatcaaga ccacctcctc gatcgagttc 1500

gcccggctgc agtttacgta taaccacata cagcgccacg tgaacgacat gctggggcgc 1560

atcgccgtcg cgtggtgcga gctgcagaac cacgagctga ctctctggaa cgaggcccgc 1620

aagctcaacc ccaacgccat cgcctccgcc accgtcggcc ggcgggtgag cgcgcgcatg 1680

ctcggagacg tcatggccgt ctccacgtgc gtgcccgtcg ccccggacaa cgtgatcgtg 1740

cagaactcga tgcgcgtcag ctcgcggccg gggacgtgct acagccgccc cctggtcagc 1800

tttcggtacg aagaccaggg cccgctgatc gaggggcagc tgggcgagaa caacgagctg 1860

cgcctcaccc gcgacgcgct cgagccgtgc accgtgggcc accggcgcta cttcatcttc 1920

ggcgggggct acgtgtactt cgaggagtac gcggcctctc acgcgctgag tcgcgccgac 1980

gtcaccaccg tcagcacctt catcgacctg aacatcacca tgctggagga ccacgagttt 2040

gtgcccctgg aggtctacac gcgccacgag atcaaggaca gcggcctgct ggactacacg 2100

gaggtccagc gccgcaacca gctgcacgac ctgcgctttg ccgacatcga cacggtcatc 2160

cgcgccgacg ccaacgccgc catgttcgcg gggctgtgcg cgttcttcga ggggatgggg 2220

gacttggggc gcgcggtcgg caaggtagtc atgggagtag tggggggcgt ggtgtcggcc 2280

gtctcgggcg tgtcctcctt tatgtccaac cccttcgggg cgcttgccgt ggggctgctg 2340

gtcctggccg gcctggtcgc ggccttcttc gccttccgct acgtcctgca actgcaacgc 2400

aatcccatga aggccctgta tccgctcacc accaaggaac tcaagacttc cgaccccggg 2460

ggcgtgggcg gggaggggga ggaaggcgcg gaggggggcg ggtttgacga ggccaagttg 2520

gccgaggccc gagaaatgat ccgatatatg gctttggtgt cggccatgga gcgcacggaa 2580

cacaaggcca gaaagaaggg cacgagcgcc ctgctcagct ccaaggtcac caacatggtt 2640

ctgcgcaagc gcaacaaagc caggtactct ccgctccaca acgaggacga ggccggagac 2700

gaagacgagc tctaa 2715

<210> 74

<211> 2715

<212> DNA

<213> artificial sequence

<220>

<223> beta 30 sheet single amino acid SNP at NC_001798.2:c56152-53438

Human herpesvirus 2 strain HG52, glycoprotein B-UL 27Q 655A

1963CA-GC

<400> 74

atgcgcgggg ggggcttgat ttgcgcgctg gtcgtggggg cgctggtggc cgcggtggcg 60

tcggcggccc cggcggcccc ggcggccccc cgcgcctcgg gcggcgtggc cgcgaccgtc 120

gcggcgaacg ggggtcccgc ctcccggccg ccccccgtcc cgagccccgc gaccaccaag 180

gcccggaagc ggaaaaccaa aaagccgccc aagcggcccg aggcgacccc gccccccgac 240

gccaacgcga ccgtcgccgc cggccacgcc acgctgcgcg cgcacctgcg ggaaatcaag 300

gtcgagaacg ccgatgccca gttttacgtg tgcccgcccc cgacgggcgc cacggtggtg 360

cagtttgagc agccgcgccg ctgcccgacg cgcccggagg ggcagaacta cacggagggc 420

atcgcggtgg tcttcaagga gaacatcgcc ccgtacaaat tcaaggccac catgtactac 480

aaagacgtga ccgtgtcgca ggtgtggttc ggccaccgct actcccagtt tatggggata 540

ttcgaggacc gcgcccccgt tcccttcgag gaggtgatcg acaagattaa cgccaagggg 600

gtctgccgct ccacggccaa gtacgtgcgg aacaacatgg agaccaccgc gtttcaccgg 660

gacgaccacg agaccgacat ggagctcaag ccggcgaagg tcgccacgcg cacgagccgg 720

gggtggcaca ccaccgacct caagtacaac ccctcgcggg tggaggcgtt ccatcggtac 780

ggcacgacgg tcaactgcat cgtcgaggag gtggacgcgc ggtcggtgta cccgtacgat 840

gagtttgtgc tggcgacggg cgactttgtg tacatgtccc cgttttacgg ctaccgggag 900

gggtcgcaca ccgagcacac cagctacgcc gccgaccgct tcaagcaggt cgacggcttc 960

tacgcgcgcg acctcaccac gaaggcccgg gccacgtcgc cgacgacccg caacttgctg 1020

acgaccccca agtttaccgt ggcctgggac tgggtgccga agcgaccggc ggtctgcacc 1080

atgaccaagt ggcaggaggt ggacgagatg ctccgcgccg agtacggcgg ctccttccgc 1140

ttctcctccg acgccatctc gaccaccttc accaccaacc tgaccgagta ctcgctctcg 1200

cgcgtcgacc tgggcgactg catcggccgg gatgcccgcg aggccatcga ccgcatgttt 1260

gcgcgcaagt acaacgccac gcacatcaag gtgggccagc cgcagtacta cctggccacg 1320

gggggcttcc tcatcgcgta ccagcccctc ctcagcaaca cgctcgccga gctgtacgtg 1380

cgggagtaca tgcgggagca ggaccgcaag ccccggaatg ccacgcccgc gccactgcgg 1440

gaggcgccca gcgccaacgc gtccgtggag cgcatcaaga ccacctcctc gatcgagttc 1500

gcccggctgc agtttacgta taaccacata cagcgccacg tgaacgacat gctggggcgc 1560

atcgccgtcg cgtggtgcga gctgcagaac cacgagctga ctctctggaa cgaggcccgc 1620

aagctcaacc ccaacgccat cgcctccgcc accgtcggcc ggcgggtgag cgcgcgcatg 1680

ctcggagacg tcatggccgt ctccacgtgc gtgcccgtcg ccccggacaa cgtgatcgtg 1740

cagaactcga tgcgcgtcag ctcgcggccg gggacgtgct acagccgccc cctggtcagc 1800

tttcggtacg aagaccaggg cccgctgatc gaggggcagc tgggcgagaa caacgagctg 1860

cgcctcaccc gcgacgcgct cgagccgtgc accgtgggcc accggcgcta cttcatcttc 1920

ggcgggggct acgtgtactt cgaggagtac gcgtactctc acgcgctgag tcgcgccgac 1980

gtcaccaccg tcagcacctt catcgacctg aacatcacca tgctggagga ccacgagttt 2040

gtgcccctgg aggtctacac gcgccacgag atcaaggaca gcggcctgct ggactacacg 2100

gaggtccagc gccgcaacca gctgcacgac ctgcgctttg ccgacatcga cacggtcatc 2160

cgcgccgacg ccaacgccgc catgttcgcg gggctgtgcg cgttcttcga ggggatgggg 2220

gacttggggc gcgcggtcgg caaggtagtc atgggagtag tggggggcgt ggtgtcggcc 2280

gtctcgggcg tgtcctcctt tatgtccaac cccttcgggg cgcttgccgt ggggctgctg 2340

gtcctggccg gcctggtcgc ggccttcttc gccttccgct acgtcctgca actgcaacgc 2400

aatcccatga aggccctgta tccgctcacc accaaggaac tcaagacttc cgaccccggg 2460

ggcgtgggcg gggaggggga ggaaggcgcg gaggggggcg ggtttgacga ggccaagttg 2520

gccgaggccc gagaaatgat ccgatatatg gctttggtgt cggccatgga gcgcacggaa 2580

cacaaggcca gaaagaaggg cacgagcgcc ctgctcagct ccaaggtcac caacatggtt 2640

ctgcgcaagc gcaacaaagc caggtactct ccgctccaca acgaggacga ggccggagac 2700

gaagacgagc tctaa 2715

<210> 75

<211> 2796

<212> DNA

<213> artificial sequence

<220>

<223> beta 23-sheet double amino acid SNPS, at NC_001348.1:56819-59614

Human herpesvirus 3 genome, glycoprotein gB Q596A N597A 1786CA-GC

1788AA-GC

<400> 75

atgtcccctt gtggctatta ttcaaagtgg agaaacaggg atcgaccaga ataccgtcgt 60

aatctacgat tcagacgttt tttctcttct atacacccta atgcagcggc tggctccgga 120

ttcaacggac ccggcgtttt cataacctcc gttacggggg tgtggttatg ctttttatgc 180

atattttcta tgtttgttac ggcggttgtg tcggtctctc caagctcgtt ttatgagagt 240

ttacaagtag agcccacaca atcagaagat ataacccggt ctgctcatct gggcgatggt 300

gatgaaatca gagaagctat acacaagtcc caggacgccg aaacaaaacc cacgttttac 360

gtctgcccac cgccaacagg ctccacaatc gtacgattag aaccaactcg gacatgtccg 420

gattatcacc ttggtaaaaa ctttacagag ggtattgctg ttgtttataa agaaaacatt 480

gcagcgtaca agtttaaggc gacggtatat tacaaagatg ttatcgttag cacggcgtgg 540

gccggaagtt cttatacgca aattactaat agatatgcgg atagggtacc aattcccgtt 600

tcagagatca cggacaccat tgataagttt ggcaagtgtt cttctaaagc aacgtacgta 660

cgaaataacc acaaagttga agcctttaat gaggataaaa atccacagga tatgcctcta 720

atcgcatcaa aatataattc tgtgggatcc aaagcatggc atactaccaa tgacacgtac 780

atggttgccg gaacccccgg aacatatagg acgggcacgt cggtgaattg catcattgag 840

gaagttgaag ccagatcaat attcccttat gatagttttg gactttccac gggagatata 900

atatacatgt ccccgttttt tggcctacgg gatggtgcat acagagaaca ttccaattat 960

gcaatggatc gttttcacca gtttgagggt tatagacaaa gggatcttga cactagagca 1020

ttactggaac ctgcagcgcg gaacttttta gtcacgcctc atttaacggt tggttggaac 1080

tggaagccaa aacgaacgga agtttgttcg cttgtcaagt ggcgtgaggt tgaagacgta 1140

gttcgcgatg agtatgcaca caattttcgc tttacaatga aaacactttc taccacgttt 1200

ataagtgaaa caaacgagtt taatcttaac caaatccatc tcagtcaatg tgtaaaggag 1260

gaagcccggg ctattattaa ccggatctat acaaccagat acaactcatc tcatgttaga 1320

accggggata tccagaccta ccttgccaga ggggggtttg ttgtggtgtt tcaacccctg 1380

ctgagcaatt ccctcgcccg tctctatctc caagaattgg tccgtgaaaa cactaatcat 1440

tcaccacaaa aacacccgac tcgaaatacc agatcccgac gaagcgtgcc agttgagttg 1500

cgtgccaata gaacaataac aaccacctca tcggtggaat ttgctatgct ccagtttaca 1560

tatgaccaca ttcaagagca tgttaatgaa atgttggcac gtatctcctc gtcgtggtgc 1620

cagctacaaa atcgcgaacg cgccctttgg agcggactat ttccaattaa cccaagtgct 1680

ttagcgagca ccattttgga tcaacgtgtt aaagctcgta ttctcggcga cgttatctcc 1740

gtttctaatt gtccagaact gggatcagat acacgcatta tacttgcagc ctctatgagg 1800

gtatctggta gtactacgcg ttgttatagc cgtcctttaa tttcaatagt tagtttaaat 1860

gggtccggga cggtggaggg ccagcttgga acagataacg agttaattat gtccagagat 1920

ctgttagaac catgcgtggc taatcacaag cgatattttc tatttgggca tcactacgta 1980

tattatgagg attatcgtta cgtccgtgaa atcgcagtcc atgatgtggg aatgattagc 2040

acttacgtag atttaaactt aacacttctt aaagatagag agtttatgcc gctgcaagta 2100

tatacaagag acgagctgcg ggatacagga ttactagact acagtgaaat tcaacgccga 2160

aatcaaatgc attcgctgcg tttttatgac atagacaagg ttgtgcaata tgatagcgga 2220

acggccatta tgcagggcat ggctcagttt ttccagggac ttgggaccgc gggccaggcc 2280

gttggacatg tggttcttgg ggccacggga gcgctgcttt ccaccgtaca cggatttacc 2340

acgtttttat ctaacccatt tggggcattg gccgtgggat tattggtttt ggcgggactg 2400

gtagcggcct tttttgcgta ccggtacgtg cttaaactta aaacaagccc gatgaaggca 2460

ttatatccac tcacaaccaa ggggttaaaa cagttaccgg aaggaatgga tccctttgcc 2520

gagaaaccca acgctactga taccccaata gaagaaattg gcgactcaca aaacactgaa 2580

ccgtcggtaa atagcgggtt tgatcccgat aaatttcgag aagcccagga aatgattaaa 2640

tatatgacgt tagtatctgc ggctgagcgc caagaatcta aagcccgcaa aaaaaataag 2700

actagcgccc ttttaacttc acgtcttacc ggccttgctt tacgaaatcg ccgaggatac 2760

tcccgtgttc gcaccgagaa tgtaacgggg gtgtaa 2796

<210> 76

<211> 2796

<212> DNA

<213> artificial sequence

<220>

<223> beta 23 sheet single amino acid SNP at NC_001348.1:56819-59614

Human herpesvirus 3 genome, glycoprotein gB N597A 1789AA-GC

<400> 76

atgtcccctt gtggctatta ttcaaagtgg agaaacaggg atcgaccaga ataccgtcgt 60

aatctacgat tcagacgttt tttctcttct atacacccta atgcagcggc tggctccgga 120

ttcaacggac ccggcgtttt cataacctcc gttacggggg tgtggttatg ctttttatgc 180

atattttcta tgtttgttac ggcggttgtg tcggtctctc caagctcgtt ttatgagagt 240

ttacaagtag agcccacaca atcagaagat ataacccggt ctgctcatct gggcgatggt 300

gatgaaatca gagaagctat acacaagtcc caggacgccg aaacaaaacc cacgttttac 360

gtctgcccac cgccaacagg ctccacaatc gtacgattag aaccaactcg gacatgtccg 420

gattatcacc ttggtaaaaa ctttacagag ggtattgctg ttgtttataa agaaaacatt 480

gcagcgtaca agtttaaggc gacggtatat tacaaagatg ttatcgttag cacggcgtgg 540

gccggaagtt cttatacgca aattactaat agatatgcgg atagggtacc aattcccgtt 600

tcagagatca cggacaccat tgataagttt ggcaagtgtt cttctaaagc aacgtacgta 660

cgaaataacc acaaagttga agcctttaat gaggataaaa atccacagga tatgcctcta 720

atcgcatcaa aatataattc tgtgggatcc aaagcatggc atactaccaa tgacacgtac 780

atggttgccg gaacccccgg aacatatagg acgggcacgt cggtgaattg catcattgag 840

gaagttgaag ccagatcaat attcccttat gatagttttg gactttccac gggagatata 900

atatacatgt ccccgttttt tggcctacgg gatggtgcat acagagaaca ttccaattat 960

gcaatggatc gttttcacca gtttgagggt tatagacaaa gggatcttga cactagagca 1020

ttactggaac ctgcagcgcg gaacttttta gtcacgcctc atttaacggt tggttggaac 1080

tggaagccaa aacgaacgga agtttgttcg cttgtcaagt ggcgtgaggt tgaagacgta 1140

gttcgcgatg agtatgcaca caattttcgc tttacaatga aaacactttc taccacgttt 1200

ataagtgaaa caaacgagtt taatcttaac caaatccatc tcagtcaatg tgtaaaggag 1260

gaagcccggg ctattattaa ccggatctat acaaccagat acaactcatc tcatgttaga 1320

accggggata tccagaccta ccttgccaga ggggggtttg ttgtggtgtt tcaacccctg 1380

ctgagcaatt ccctcgcccg tctctatctc caagaattgg tccgtgaaaa cactaatcat 1440

tcaccacaaa aacacccgac tcgaaatacc agatcccgac gaagcgtgcc agttgagttg 1500

cgtgccaata gaacaataac aaccacctca tcggtggaat ttgctatgct ccagtttaca 1560

tatgaccaca ttcaagagca tgttaatgaa atgttggcac gtatctcctc gtcgtggtgc 1620

cagctacaaa atcgcgaacg cgccctttgg agcggactat ttccaattaa cccaagtgct 1680

ttagcgagca ccattttgga tcaacgtgtt aaagctcgta ttctcggcga cgttatctcc 1740

gtttctaatt gtccagaact gggatcagat acacgcatta tacttcaagc ctctatgagg 1800

gtatctggta gtactacgcg ttgttatagc cgtcctttaa tttcaatagt tagtttaaat 1860

gggtccggga cggtggaggg ccagcttgga acagataacg agttaattat gtccagagat 1920

ctgttagaac catgcgtggc taatcacaag cgatattttc tatttgggca tcactacgta 1980

tattatgagg attatcgtta cgtccgtgaa atcgcagtcc atgatgtggg aatgattagc 2040

acttacgtag atttaaactt aacacttctt aaagatagag agtttatgcc gctgcaagta 2100

tatacaagag acgagctgcg ggatacagga ttactagact acagtgaaat tcaacgccga 2160

aatcaaatgc attcgctgcg tttttatgac atagacaagg ttgtgcaata tgatagcgga 2220

acggccatta tgcagggcat ggctcagttt ttccagggac ttgggaccgc gggccaggcc 2280

gttggacatg tggttcttgg ggccacggga gcgctgcttt ccaccgtaca cggatttacc 2340

acgtttttat ctaacccatt tggggcattg gccgtgggat tattggtttt ggcgggactg 2400

gtagcggcct tttttgcgta ccggtacgtg cttaaactta aaacaagccc gatgaaggca 2460

ttatatccac tcacaaccaa ggggttaaaa cagttaccgg aaggaatgga tccctttgcc 2520

gagaaaccca acgctactga taccccaata gaagaaattg gcgactcaca aaacactgaa 2580

ccgtcggtaa atagcgggtt tgatcccgat aaatttcgag aagcccagga aatgattaaa 2640

tatatgacgt tagtatctgc ggctgagcgc caagaatcta aagcccgcaa aaaaaataag 2700

actagcgccc ttttaacttc acgtcttacc ggccttgctt tacgaaatcg ccgaggatac 2760

tcccgtgttc gcaccgagaa tgtaacgggg gtgtaa 2796

<210> 77

<211> 2796

<212> DNA

<213> artificial sequence

<220>

<223> beta 30 sheet double amino acid SNP, at NC_001348.1:56819-59614

Human herpesvirus 3 genome, glycoprotein gB Y667A E670A 1999TA-GC

2009A-C

<400> 77

atgtcccctt gtggctatta ttcaaagtgg agaaacaggg atcgaccaga ataccgtcgt 60

aatctacgat tcagacgttt tttctcttct atacacccta atgcagcggc tggctccgga 120

ttcaacggac ccggcgtttt cataacctcc gttacggggg tgtggttatg ctttttatgc 180

atattttcta tgtttgttac ggcggttgtg tcggtctctc caagctcgtt ttatgagagt 240

ttacaagtag agcccacaca atcagaagat ataacccggt ctgctcatct gggcgatggt 300

gatgaaatca gagaagctat acacaagtcc caggacgccg aaacaaaacc cacgttttac 360

gtctgcccac cgccaacagg ctccacaatc gtacgattag aaccaactcg gacatgtccg 420

gattatcacc ttggtaaaaa ctttacagag ggtattgctg ttgtttataa agaaaacatt 480

gcagcgtaca agtttaaggc gacggtatat tacaaagatg ttatcgttag cacggcgtgg 540

gccggaagtt cttatacgca aattactaat agatatgcgg atagggtacc aattcccgtt 600

tcagagatca cggacaccat tgataagttt ggcaagtgtt cttctaaagc aacgtacgta 660

cgaaataacc acaaagttga agcctttaat gaggataaaa atccacagga tatgcctcta 720

atcgcatcaa aatataattc tgtgggatcc aaagcatggc atactaccaa tgacacgtac 780

atggttgccg gaacccccgg aacatatagg acgggcacgt cggtgaattg catcattgag 840

gaagttgaag ccagatcaat attcccttat gatagttttg gactttccac gggagatata 900

atatacatgt ccccgttttt tggcctacgg gatggtgcat acagagaaca ttccaattat 960

gcaatggatc gttttcacca gtttgagggt tatagacaaa gggatcttga cactagagca 1020

ttactggaac ctgcagcgcg gaacttttta gtcacgcctc atttaacggt tggttggaac 1080

tggaagccaa aacgaacgga agtttgttcg cttgtcaagt ggcgtgaggt tgaagacgta 1140

gttcgcgatg agtatgcaca caattttcgc tttacaatga aaacactttc taccacgttt 1200

ataagtgaaa caaacgagtt taatcttaac caaatccatc tcagtcaatg tgtaaaggag 1260

gaagcccggg ctattattaa ccggatctat acaaccagat acaactcatc tcatgttaga 1320

accggggata tccagaccta ccttgccaga ggggggtttg ttgtggtgtt tcaacccctg 1380

ctgagcaatt ccctcgcccg tctctatctc caagaattgg tccgtgaaaa cactaatcat 1440

tcaccacaaa aacacccgac tcgaaatacc agatcccgac gaagcgtgcc agttgagttg 1500

cgtgccaata gaacaataac aaccacctca tcggtggaat ttgctatgct ccagtttaca 1560

tatgaccaca ttcaagagca tgttaatgaa atgttggcac gtatctcctc gtcgtggtgc 1620

cagctacaaa atcgcgaacg cgccctttgg agcggactat ttccaattaa cccaagtgct 1680

ttagcgagca ccattttgga tcaacgtgtt aaagctcgta ttctcggcga cgttatctcc 1740

gtttctaatt gtccagaact gggatcagat acacgcatta tacttcaaaa ctctatgagg 1800

gtatctggta gtactacgcg ttgttatagc cgtcctttaa tttcaatagt tagtttaaat 1860

gggtccggga cggtggaggg ccagcttgga acagataacg agttaattat gtccagagat 1920

ctgttagaac catgcgtggc taatcacaag cgatattttc tatttgggca tcactacgta 1980

tattatgagg attatcgtgc cgtccgtgca atcgcagtcc atgatgtggg aatgattagc 2040

acttacgtag atttaaactt aacacttctt aaagatagag agtttatgcc gctgcaagta 2100

tatacaagag acgagctgcg ggatacagga ttactagact acagtgaaat tcaacgccga 2160

aatcaaatgc attcgctgcg tttttatgac atagacaagg ttgtgcaata tgatagcgga 2220

acggccatta tgcagggcat ggctcagttt ttccagggac ttgggaccgc gggccaggcc 2280

gttggacatg tggttcttgg ggccacggga gcgctgcttt ccaccgtaca cggatttacc 2340

acgtttttat ctaacccatt tggggcattg gccgtgggat tattggtttt ggcgggactg 2400

gtagcggcct tttttgcgta ccggtacgtg cttaaactta aaacaagccc gatgaaggca 2460

ttatatccac tcacaaccaa ggggttaaaa cagttaccgg aaggaatgga tccctttgcc 2520

gagaaaccca acgctactga taccccaata gaagaaattg gcgactcaca aaacactgaa 2580

ccgtcggtaa atagcgggtt tgatcccgat aaatttcgag aagcccagga aatgattaaa 2640

tatatgacgt tagtatctgc ggctgagcgc caagaatcta aagcccgcaa aaaaaataag 2700

actagcgccc ttttaacttc acgtcttacc ggccttgctt tacgaaatcg ccgaggatac 2760

tcccgtgttc gcaccgagaa tgtaacgggg gtgtaa 2796

<210> 78

<211> 2796

<212> DNA

<213> artificial sequence

<220>

<223> beta 30 sheet single amino acid SNP at NC_001348.1:56819-59614

Human herpesvirus 3 genome, glycoprotein gB E670a 2009A-C

<400> 78

atgtcccctt gtggctatta ttcaaagtgg agaaacaggg atcgaccaga ataccgtcgt 60

aatctacgat tcagacgttt tttctcttct atacacccta atgcagcggc tggctccgga 120

ttcaacggac ccggcgtttt cataacctcc gttacggggg tgtggttatg ctttttatgc 180

atattttcta tgtttgttac ggcggttgtg tcggtctctc caagctcgtt ttatgagagt 240

ttacaagtag agcccacaca atcagaagat ataacccggt ctgctcatct gggcgatggt 300

gatgaaatca gagaagctat acacaagtcc caggacgccg aaacaaaacc cacgttttac 360

gtctgcccac cgccaacagg ctccacaatc gtacgattag aaccaactcg gacatgtccg 420

gattatcacc ttggtaaaaa ctttacagag ggtattgctg ttgtttataa agaaaacatt 480

gcagcgtaca agtttaaggc gacggtatat tacaaagatg ttatcgttag cacggcgtgg 540

gccggaagtt cttatacgca aattactaat agatatgcgg atagggtacc aattcccgtt 600

tcagagatca cggacaccat tgataagttt ggcaagtgtt cttctaaagc aacgtacgta 660

cgaaataacc acaaagttga agcctttaat gaggataaaa atccacagga tatgcctcta 720

atcgcatcaa aatataattc tgtgggatcc aaagcatggc atactaccaa tgacacgtac 780

atggttgccg gaacccccgg aacatatagg acgggcacgt cggtgaattg catcattgag 840

gaagttgaag ccagatcaat attcccttat gatagttttg gactttccac gggagatata 900

atatacatgt ccccgttttt tggcctacgg gatggtgcat acagagaaca ttccaattat 960

gcaatggatc gttttcacca gtttgagggt tatagacaaa gggatcttga cactagagca 1020

ttactggaac ctgcagcgcg gaacttttta gtcacgcctc atttaacggt tggttggaac 1080

tggaagccaa aacgaacgga agtttgttcg cttgtcaagt ggcgtgaggt tgaagacgta 1140

gttcgcgatg agtatgcaca caattttcgc tttacaatga aaacactttc taccacgttt 1200

ataagtgaaa caaacgagtt taatcttaac caaatccatc tcagtcaatg tgtaaaggag 1260

gaagcccggg ctattattaa ccggatctat acaaccagat acaactcatc tcatgttaga 1320

accggggata tccagaccta ccttgccaga ggggggtttg ttgtggtgtt tcaacccctg 1380

ctgagcaatt ccctcgcccg tctctatctc caagaattgg tccgtgaaaa cactaatcat 1440

tcaccacaaa aacacccgac tcgaaatacc agatcccgac gaagcgtgcc agttgagttg 1500

cgtgccaata gaacaataac aaccacctca tcggtggaat ttgctatgct ccagtttaca 1560

tatgaccaca ttcaagagca tgttaatgaa atgttggcac gtatctcctc gtcgtggtgc 1620

cagctacaaa atcgcgaacg cgccctttgg agcggactat ttccaattaa cccaagtgct 1680

ttagcgagca ccattttgga tcaacgtgtt aaagctcgta ttctcggcga cgttatctcc 1740

gtttctaatt gtccagaact gggatcagat acacgcatta tacttcaaaa ctctatgagg 1800

gtatctggta gtactacgcg ttgttatagc cgtcctttaa tttcaatagt tagtttaaat 1860

gggtccggga cggtggaggg ccagcttgga acagataacg agttaattat gtccagagat 1920

ctgttagaac catgcgtggc taatcacaag cgatattttc tatttgggca tcactacgta 1980

tattatgagg attatcgtta cgtccgtgca atcgcagtcc atgatgtggg aatgattagc 2040

acttacgtag atttaaactt aacacttctt aaagatagag agtttatgcc gctgcaagta 2100

tatacaagag acgagctgcg ggatacagga ttactagact acagtgaaat tcaacgccga 2160

aatcaaatgc attcgctgcg tttttatgac atagacaagg ttgtgcaata tgatagcgga 2220

acggccatta tgcagggcat ggctcagttt ttccagggac ttgggaccgc gggccaggcc 2280

gttggacatg tggttcttgg ggccacggga gcgctgcttt ccaccgtaca cggatttacc 2340

acgtttttat ctaacccatt tggggcattg gccgtgggat tattggtttt ggcgggactg 2400

gtagcggcct tttttgcgta ccggtacgtg cttaaactta aaacaagccc gatgaaggca 2460

ttatatccac tcacaaccaa ggggttaaaa cagttaccgg aaggaatgga tccctttgcc 2520

gagaaaccca acgctactga taccccaata gaagaaattg gcgactcaca aaacactgaa 2580

ccgtcggtaa atagcgggtt tgatcccgat aaatttcgag aagcccagga aatgattaaa 2640

tatatgacgt tagtatctgc ggctgagcgc caagaatcta aagcccgcaa aaaaaataag 2700

actagcgccc ttttaacttc acgtcttacc ggccttgctt tacgaaatcg ccgaggatac 2760

tcccgtgttc gcaccgagaa tgtaacgggg gtgtaa 2796

<210> 79

<211> 2574

<212> DNA

<213> artificial sequence

<220>

<223> beta 30 sheet double amino acid SNP, at NC_009334.1:c160348-157775

Human herpesvirus 4 genome, glycoprotein B BALF4 strain AG76

1900tt-gc 2013a-c F611A E615A

<400> 79

atgactcggc gtagggtgct aagcgtggtc gtgctgctag ccgccctggc gtgccgcctc 60

ggtgcgcaga ccccagagca gcccgcaccc cccgccacca cggtgcagcc taccgccacg 120

cgtcagcaaa ccagctttcc tttccgagtc tgcgagctct ccagccacgg cgacctgttc 180

cgcttctcct cggacatcca gtgtccctcg tttggcacgc gggagaatca cacggagggc 240

ctgttgatgg tgtttaaaga caacattatt ccctactcgt ttaaggtccg ctcctacacc 300

aagatagtga ccaacattct catctacaat ggctggtacg cggactccgt gaccaaccgg 360

cacgaggaga agttctccgt tgacagctac gaaactgacc agatggatac catctaccag 420

tgctacaacg cggtcaagat gacaaaagat gggctgacgc gcgtgtatgt agaccgcgac 480

ggagttaaca tcaccgtcaa cctaaagccc accgggggcc tggccaacgg ggtgcgccgc 540

tacgccagcc agacggagct ctatgacgcc cccgggtggt tgatatggac ttacagaaca 600

agaactaccg tcaactgcct gataactgac atgatggcca agtccaacag ccccttcgac 660

ttctttgtga ccaccaccgg gcagactgtg gaaatgtccc ctttctatga cgggaaaaat 720

aaggaaacct tccatgagcg ggcagactcc ttccacgtga gaactaacta caagatagtg 780

gactacgaca accgagggac gaacccgcaa ggcgaacgcc gagccttcct ggacaagggc 840

acttacaccc tatcttggaa gctcgagaac aggacagcct actgcccgct tcaacactgg 900

caaacctttg actcgaccat cgccacagaa acagggaagt caatacattt tgtgactgac 960

gagggcacct ctagcttcgt gaccaacaca accgtgggca tagagctccc ggacgccttc 1020

aagtgcatcg aagagcaggt gaacaagacc atgcatgaga agtacgaggc cgtccaggat 1080

cgttacacga agggccagga agccattaca tattttataa cgagcggagg attgttatta 1140

gcttggctac ctctgacccc gcgctcgttg gccaccgtca agaacctgac ggagcttacc 1200

actccgactt cctcaccccc cagcagtcca tcgccccccg ccccacccgc ggcccgcggg 1260

agcacctccg ccgccgttct gaggcgccgg aggcgggatg cggggaatgc caccacaccg 1320

gtgccccccg cggcccccgg gaagtccctg ggcaccctca acaatcccgc caccgtccag 1380

atccaatttg cctacgattc cctgcgccgc cagatcaacc gcatgctggg agacctcgcg 1440

cgggcctggt gcctggagca gaagaggcag aacatggtgc tgagagaact aaccaagatt 1500

aatcccacca ccgtcatgtc cagcatctac ggtaaggcgg tggcggccaa gcgcctgggg 1560

gatgtcatct cagtctccca gtgcgtgccc gttaaccagg ccaccgtcac cctgcgcaag 1620

agcatgaggg tccctggctc cgagaccatg tgctactcgc gccccctggt gtccttcagc 1680

tttatcaacg acaccaagac ctacgaggga cagctgggca ccgacaacga gatcttcctc 1740

acaaaaaaga tgacggaggt gtgccaggcg accagccagt actacttcca gtccggcaac 1800

gagatccacg tctacaacga ctaccaccac gctaaaacca tcgcgctgga cggcattgcc 1860

accctgcaga ccttcatctc actaaacacc tccctcatcg agaacattga ctttgcctcc 1920

ctggagctgt actcacggga cgaacagcgt gcctccaacg tctttgacct ggagggcatc 1980

ttccgggagt acaacttcca ggcgcaaaac atcgccggcc tgcggaagga tttggacaat 2040

gcagtgtcaa acggaagaaa tcaattcgtg gacggcctgg gggaacttat ggacagtctg 2100

ggtagcgtgg gtcagtccat caccaaccta gtcagcacgg tggggggttt gtttagcagc 2160

ctggtctctg gtttcatctc cttcttcaaa aaccccttcg gcggcatgct cattctggtc 2220

ctggtggcgg gggtggtgat cctggttatt tccctcacga ggcgcacgcg ccagatgtcg 2280

cagcagccgg tgcagatgct ctaccccggg atcgacgagc tcgctcagca acatgcctct 2340

ggtgagggtc caggcattaa tcccattagt aagacagaat tacaagccat catgttagcg 2400

ctgcatgagc aaaaccagga gcaaaagaga gcagctcaga gggcggccgg accctcagtg 2460

gccagcagag cattgcaggc agccagggac cgttttccag gcctacgcag aagacgctat 2520

cacgatccag agaccgccgc cgcactgctt ggggaggcag agactgagtt ttaa 2574

<210> 80

<211> 2574

<212> DNA

<213> artificial sequence

<220>

<223> beta 30 sheet single amino acid SNP at NC_009334.1:c160348-157775

Human herpesvirus 4 genome, glycoprotein B BALF4 strain AG76

2013a-c E615A

<400> 80

atgactcggc gtagggtgct aagcgtggtc gtgctgctag ccgccctggc gtgccgcctc 60

ggtgcgcaga ccccagagca gcccgcaccc cccgccacca cggtgcagcc taccgccacg 120

cgtcagcaaa ccagctttcc tttccgagtc tgcgagctct ccagccacgg cgacctgttc 180

cgcttctcct cggacatcca gtgtccctcg tttggcacgc gggagaatca cacggagggc 240

ctgttgatgg tgtttaaaga caacattatt ccctactcgt ttaaggtccg ctcctacacc 300

aagatagtga ccaacattct catctacaat ggctggtacg cggactccgt gaccaaccgg 360

cacgaggaga agttctccgt tgacagctac gaaactgacc agatggatac catctaccag 420

tgctacaacg cggtcaagat gacaaaagat gggctgacgc gcgtgtatgt agaccgcgac 480

ggagttaaca tcaccgtcaa cctaaagccc accgggggcc tggccaacgg ggtgcgccgc 540

tacgccagcc agacggagct ctatgacgcc cccgggtggt tgatatggac ttacagaaca 600

agaactaccg tcaactgcct gataactgac atgatggcca agtccaacag ccccttcgac 660

ttctttgtga ccaccaccgg gcagactgtg gaaatgtccc ctttctatga cgggaaaaat 720

aaggaaacct tccatgagcg ggcagactcc ttccacgtga gaactaacta caagatagtg 780

gactacgaca accgagggac gaacccgcaa ggcgaacgcc gagccttcct ggacaagggc 840

acttacaccc tatcttggaa gctcgagaac aggacagcct actgcccgct tcaacactgg 900

caaacctttg actcgaccat cgccacagaa acagggaagt caatacattt tgtgactgac 960

gagggcacct ctagcttcgt gaccaacaca accgtgggca tagagctccc ggacgccttc 1020

aagtgcatcg aagagcaggt gaacaagacc atgcatgaga agtacgaggc cgtccaggat 1080

cgttacacga agggccagga agccattaca tattttataa cgagcggagg attgttatta 1140

gcttggctac ctctgacccc gcgctcgttg gccaccgtca agaacctgac ggagcttacc 1200

actccgactt cctcaccccc cagcagtcca tcgccccccg ccccacccgc ggcccgcggg 1260

agcacctccg ccgccgttct gaggcgccgg aggcgggatg cggggaatgc caccacaccg 1320

gtgccccccg cggcccccgg gaagtccctg ggcaccctca acaatcccgc caccgtccag 1380

atccaatttg cctacgattc cctgcgccgc cagatcaacc gcatgctggg agacctcgcg 1440

cgggcctggt gcctggagca gaagaggcag aacatggtgc tgagagaact aaccaagatt 1500

aatcccacca ccgtcatgtc cagcatctac ggtaaggcgg tggcggccaa gcgcctgggg 1560

gatgtcatct cagtctccca gtgcgtgccc gttaaccagg ccaccgtcac cctgcgcaag 1620

agcatgaggg tccctggctc cgagaccatg tgctactcgc gccccctggt gtccttcagc 1680

tttatcaacg acaccaagac ctacgaggga cagctgggca ccgacaacga gatcttcctc 1740

acaaaaaaga tgacggaggt gtgccaggcg accagccagt actacttcca gtccggcaac 1800

gagatccacg tctacaacga ctaccaccac tttaaaacca tcgcgctgga cggcattgcc 1860

accctgcaga ccttcatctc actaaacacc tccctcatcg agaacattga ctttgcctcc 1920

ctggagctgt actcacggga cgaacagcgt gcctccaacg tctttgacct ggagggcatc 1980

ttccgggagt acaacttcca ggcgcaaaac atcgccggcc tgcggaagga tttggacaat 2040

gcagtgtcaa acggaagaaa tcaattcgtg gacggcctgg gggaacttat ggacagtctg 2100

ggtagcgtgg gtcagtccat caccaaccta gtcagcacgg tggggggttt gtttagcagc 2160

ctggtctctg gtttcatctc cttcttcaaa aaccccttcg gcggcatgct cattctggtc 2220

ctggtggcgg gggtggtgat cctggttatt tccctcacga ggcgcacgcg ccagatgtcg 2280

cagcagccgg tgcagatgct ctaccccggg atcgacgagc tcgctcagca acatgcctct 2340

ggtgagggtc caggcattaa tcccattagt aagacagaat tacaagccat catgttagcg 2400

ctgcatgagc aaaaccagga gcaaaagaga gcagctcaga gggcggccgg accctcagtg 2460

gccagcagag cattgcaggc agccagggac cgttttccag gcctacgcag aagacgctat 2520

cacgatccag agaccgccgc cgcactgctt ggggaggcag agactgagtt ttaa 2574

<210> 81

<211> 2724

<212> DNA

<213> artificial sequence

<220>

<223> beta 30 sheet double amino acid SNP, at NC_006273.2:c84789-82066

Human herpesvirus 5-strain Merlin genome UL55 gB 1896tt-gc

1913a-c F633A D638A

<400> 81

atggaatcca ggatctggtg cctggtagtc tgcgttaact tgtgtatcgt ctgtctgggt 60

gctgcggttt cctcatcttc tactcgtgga acttctgcta ctcacagtca ccattcctct 120

catacgacgt ctgctgctca ctctcgatcc ggttcagtct ctcaacgcgt aacttcttcc 180

caaacggtca gccatggtgt taacgagacc atctacaaca ctaccctcaa gtacggagat 240

gtggtggggg tcaataccac caagtacccc tatcgcgtgt gttctatggc ccagggtacg 300

gatcttattc gctttgaacg taatatcgtc tgcacctcga tgaagcccat caatgaagac 360

ctggacgagg gcatcatggt ggtctacaaa cgcaacatcg tcgcgcacac ctttaaggta 420

cgagtctacc agaaggtttt gacgtttcgt cgtagctacg cttacatcca caccacttat 480

ctgctgggca gcaacacgga atacgtggcg cctcctatgt gggagattca tcatatcaac 540

agccacagtc agtgctacag ttcctacagc cgcgttatag caggcacggt tttcgtggct 600

tatcataggg acagctatga aaacaaaacc atgcaattaa tgcccgacga ttattccaac 660

acccacagta cccgttacgt gacggtcaag gatcaatggc acagccgcgg cagcacctgg 720

ctctatcgtg agacctgtaa tctgaattgt atggtgacca tcactactgc gcgctccaaa 780

tatccttatc attttttcgc cacttccacg ggtgacgtgg ttgacatttc tcctttctac 840

aacggaacca atcgcaatgc cagctacttt ggagaaaacg ccgacaagtt tttcattttt 900

ccgaactaca ctatcgtctc cgactttgga agaccgaatt ctgcgttaga gacccacagg 960

ttggtggctt ttcttgaacg tgcggactcg gtgatctcct gggatataca ggacgaaaag 1020

aatgtcactt gtcaactcac tttctgggaa gcctcggaac gcaccattcg ttccgaagcc 1080

gaggactcgt atcacttttc ttctgccaaa atgaccgcca ctttcttatc taagaagcaa 1140

gaggtgaaca tgtccgactc tgcgctggac tgcgtacgtg atgaggctat aaataagtta 1200

cagcagattt tcaatacttc atacaatcaa acatatgaaa aatatggaaa cgtgtccgtc 1260

tttgaaacca ctggtggttt ggtagtgttc tggcaaggta tcaagcaaaa atctctggtg 1320

gaactcgaac gtttggccaa ccgctccagt ctgaatctta ctcataatag aaccaaaaga 1380

agtacagatg gcaacaatgc aactcattta tccaacatgg aatcggtgca caatctggtc 1440

tacgcccagc tgcagttcac ctatgacacg ttgcgcggtt acatcaaccg ggcgctggcg 1500

caaatcgcag aagcctggtg tgtggatcaa cggcgcaccc tagaggtctt caaggaactc 1560

agcaagatca acccgtcagc cattctctcg gccatttaca acaaaccgat tgccgcgcgt 1620

ttcatgggtg atgtcttggg cctggccagc tgcgtgacca tcaaccaaac cagcgtcaag 1680

gtgctgcgtg atatgaacgt gaaggagtcg ccaggacgct gctactcacg acccgtggtc 1740

atctttaatt tcgccaacag ctcgtacgtg cagtacggtc aactgggcga ggacaacgaa 1800

atcctgttgg gcaaccaccg cactgaggaa tgtcagcttc ccagcctcaa gatcttcatc 1860

gccgggaact cggcctacga gtacgtggac tacctcgcca aacgcatgat tgccctcagc 1920

agtatctcca ccgtcgacag catgatcgcc ctggatatcg acccgctgga aaataccgac 1980

ttcagggtac tggaacttta ctcgcagaaa gagctgcgtt ccagcaacgt ttttgacctc 2040

gaagagatca tgcgcgaatt caactcgtac aagcagcggg taaagtacgt ggaggacaag 2100

gtagtcgacc cgctaccgcc ctacctcaag ggtctggacg acctcatgag cggcctgggc 2160

gccgcgggaa aggccgttgg cgtagccatt ggggccgtgg gtggcgcggt ggcctccgtg 2220

gtcgaaggcg ttgccacctt cctcaaaaac cccttcggag cgttcaccat catcctcgtg 2280

gccatagctg tagtcattat cacttatttg atctatactc gacagcggcg tttgtgcacg 2340

cagccgctgc agaacctctt tccctatctg gtgtccgccg acgggaccac cgtgacgtcg 2400

ggcagcacca aagacacgtc gttacaggct ccgccttcct acgaggaaag tgtttataat 2460

tctggtcgca aaggaccggg accaccgtcg tctgatgcat ccacggcggc tccgccttac 2520

accaacgagc aggcttacca gatgcttctg gccctggccc gtctggacgc agagcagcga 2580

gcgcagcaga acggtacaga ttctttggac ggacggactg gcacgcagga caagggacag 2640

aagcccaacc tactagaccg actgcgacat cgcaaaaacg gctaccgaca cttgaaagac 2700

tctgacgaag aagagaacgt ctga 2724

<210> 82

<211> 2724

<212> DNA

<213> artificial sequence

<220>

<223> beta 30 sheet single amino acid SNP at NC_006273.2:c84789-82066

Human herpesvirus 5-strain Merlin genome UL55 gB 1913a-c D638A

<400> 82

atggaatcca ggatctggtg cctggtagtc tgcgttaact tgtgtatcgt ctgtctgggt 60

gctgcggttt cctcatcttc tactcgtgga acttctgcta ctcacagtca ccattcctct 120

catacgacgt ctgctgctca ctctcgatcc ggttcagtct ctcaacgcgt aacttcttcc 180

caaacggtca gccatggtgt taacgagacc atctacaaca ctaccctcaa gtacggagat 240

gtggtggggg tcaataccac caagtacccc tatcgcgtgt gttctatggc ccagggtacg 300

gatcttattc gctttgaacg taatatcgtc tgcacctcga tgaagcccat caatgaagac 360

ctggacgagg gcatcatggt ggtctacaaa cgcaacatcg tcgcgcacac ctttaaggta 420

cgagtctacc agaaggtttt gacgtttcgt cgtagctacg cttacatcca caccacttat 480

ctgctgggca gcaacacgga atacgtggcg cctcctatgt gggagattca tcatatcaac 540

agccacagtc agtgctacag ttcctacagc cgcgttatag caggcacggt tttcgtggct 600

tatcataggg acagctatga aaacaaaacc atgcaattaa tgcccgacga ttattccaac 660

acccacagta cccgttacgt gacggtcaag gatcaatggc acagccgcgg cagcacctgg 720

ctctatcgtg agacctgtaa tctgaattgt atggtgacca tcactactgc gcgctccaaa 780

tatccttatc attttttcgc cacttccacg ggtgacgtgg ttgacatttc tcctttctac 840

aacggaacca atcgcaatgc cagctacttt ggagaaaacg ccgacaagtt tttcattttt 900

ccgaactaca ctatcgtctc cgactttgga agaccgaatt ctgcgttaga gacccacagg 960

ttggtggctt ttcttgaacg tgcggactcg gtgatctcct gggatataca ggacgaaaag 1020

aatgtcactt gtcaactcac tttctgggaa gcctcggaac gcaccattcg ttccgaagcc 1080

gaggactcgt atcacttttc ttctgccaaa atgaccgcca ctttcttatc taagaagcaa 1140

gaggtgaaca tgtccgactc tgcgctggac tgcgtacgtg atgaggctat aaataagtta 1200

cagcagattt tcaatacttc atacaatcaa acatatgaaa aatatggaaa cgtgtccgtc 1260

tttgaaacca ctggtggttt ggtagtgttc tggcaaggta tcaagcaaaa atctctggtg 1320

gaactcgaac gtttggccaa ccgctccagt ctgaatctta ctcataatag aaccaaaaga 1380

agtacagatg gcaacaatgc aactcattta tccaacatgg aatcggtgca caatctggtc 1440

tacgcccagc tgcagttcac ctatgacacg ttgcgcggtt acatcaaccg ggcgctggcg 1500

caaatcgcag aagcctggtg tgtggatcaa cggcgcaccc tagaggtctt caaggaactc 1560

agcaagatca acccgtcagc cattctctcg gccatttaca acaaaccgat tgccgcgcgt 1620

ttcatgggtg atgtcttggg cctggccagc tgcgtgacca tcaaccaaac cagcgtcaag 1680

gtgctgcgtg atatgaacgt gaaggagtcg ccaggacgct gctactcacg acccgtggtc 1740

atctttaatt tcgccaacag ctcgtacgtg cagtacggtc aactgggcga ggacaacgaa 1800

atcctgttgg gcaaccaccg cactgaggaa tgtcagcttc ccagcctcaa gatcttcatc 1860

gccgggaact cggcctacga gtacgtggac tacctcttca aacgcatgat tgccctcagc 1920

agtatctcca ccgtcgacag catgatcgcc ctggatatcg acccgctgga aaataccgac 1980

ttcagggtac tggaacttta ctcgcagaaa gagctgcgtt ccagcaacgt ttttgacctc 2040

gaagagatca tgcgcgaatt caactcgtac aagcagcggg taaagtacgt ggaggacaag 2100

gtagtcgacc cgctaccgcc ctacctcaag ggtctggacg acctcatgag cggcctgggc 2160

gccgcgggaa aggccgttgg cgtagccatt ggggccgtgg gtggcgcggt ggcctccgtg 2220

gtcgaaggcg ttgccacctt cctcaaaaac cccttcggag cgttcaccat catcctcgtg 2280

gccatagctg tagtcattat cacttatttg atctatactc gacagcggcg tttgtgcacg 2340

cagccgctgc agaacctctt tccctatctg gtgtccgccg acgggaccac cgtgacgtcg 2400

ggcagcacca aagacacgtc gttacaggct ccgccttcct acgaggaaag tgtttataat 2460

tctggtcgca aaggaccggg accaccgtcg tctgatgcat ccacggcggc tccgccttac 2520

accaacgagc aggcttacca gatgcttctg gccctggccc gtctggacgc agagcagcga 2580

gcgcagcaga acggtacaga ttctttggac ggacggactg gcacgcagga caagggacag 2640

aagcccaacc tactagaccg actgcgacat cgcaaaaacg gctaccgaca cttgaaagac 2700

tctgacgaag aagagaacgt ctga 2724

<210> 83

<211> 2423

<212> DNA

<213> artificial sequence

<220>

<223> beta 30 sheet double amino acid SNP at NC_001664.4:c62129-59637

Human beta herpesvirus 6A, variant A genome, strain U1102 gB U39

Gene 1708ca-gc 1730a-c H671A E678A

<400> 83

cggatcatta tatcagagcg ggctataatc acaaatatcc ttttcggatt tgttcgattg 60

ccaaaggcac ggatttaatg cggttcgaca gagatatttc gtgctcgccg tataagtcta 120

atgcaaagat gtcggagggt tttttcatca tttacaaaac aaatatcgag acctacactt 180

ttccagtgag aacgtataaa aaagagttga cgttccaaag tagttaccgt gatgtgggtg 240

tggtttattt tctggatcgg acggtgatgg gtttggccat gccggtgtac gaagcaaatt 300

tagttaattc tcatgcgcag tgttattccg ccgtagcgat gaaacgaccc gatggtacgg 360

tgtttagtgc ctttcatgag gataataata aaaacaatac tctaaattta tttcctctga 420

atttcaaatc tataactaat aaaagattta tcactacgaa agaaccctac tttgcaaggg 480

gtcctttgtg gctatattct acatcaacgt ctctcaattg tattgtgacg gaggctacgg 540

ctaaggcgaa atacccgttt agttactttg ctttgacgac tggcgaaatc gtggaagggt 600

ctccgttctt caacggttca aacggtaaac attttgcaga gccgttagaa aaattgacaa 660

tcttggaaaa ctatactatg atagaagatc taatgaatgg tatgaatggg gccactacgt 720

tagtgaggaa aatcgctttt ctcgagaaag cggatacttt gttttcttgg gaaatcaagg 780

aagagaatga atcggtgtgt atgctaaagc actggaccac ggtgactcac gggcttcgag 840

cggagacgaa tgagacctat cactttatct ctaaggagtt gacagccgct ttcgtcgccc 900

ccaaggagtc cttaaatctt accgatccga aacaaacgtg tattaagaat gaatttgaaa 960

aaataattaa tgaagtctat atgtcagatt ataatgatac atatagcatg aatggtagtt 1020

atcaaatttt taagactacg ggagatttga ttttgatttg gcaacctctt gtgcaaaaat 1080

ctcttatgtt tcttgagcag ggttcggaaa aaatacgtag gaggcgagat gtgggggatg 1140

ttaagtctag acatgatatt ctttatgtgc aattacagta tctttatgat actttgaaag 1200

attatatcaa tgatgcattg gggaatttgg cagaatcttg gtgtctcgat caaaagcgaa 1260

cgataacgat gttgcacgaa cttagtaaga ttagtccgtc gagtatcgtg tctgaggttt 1320

acggtcgtcc gatatctgca cagttgcatg gtgacgtgtt agctatctcg aaatgcatag 1380

aggttaatca gtcatccgtt cagcttcata agagtatgcg ggtcgtcgat gcaaagggag 1440

taaggagtga aacgatgtgt tataatcggc ccttggtgac gtttagtttt gtgaactcga 1500

cgcctgaggt tgtccctggc cagctagggt tagataatga aattctgttg ggtgatcata 1560

ggacagagga atgtgaaata cctagtacaa agatcttttt atctggaaat catgcgcacg 1620

tgtataccga ttatacggct acgaattcga cgcccatagc agacattgag gtattggatg 1680

cttttattag actaaaaatc gatcctcttg aaaatgccga ttttaaagta ctcgatttat 1740

attcgccgga cgaattgagt agagcaaacg ttttcgatct agagaatatt cttcgtgaat 1800

ataactcata taagagcgca ctatatacta tagaagctaa aattgctacg aatacacctt 1860

cgtatgttaa tgggattaat tcttttttac aagggcttgg ggctataggc actggattgg 1920

gctcggttat aagtgttacg gcaggagcgc ttggggatat tgtgggtgga gtggtgtctt 1980

ttctaaaaaa tccattcggg ggtggtctca tgttgatttt agcgatagta gttgttgtga 2040

taataattgt ggttttcgtt agacaaagac atgtgcttag taagcctatt gacatgatgt 2100

ttccttatgc caccaatccg gtgactactg tgtccagtgt tacggggacc actgtcgtca 2160

agacacctag tgttaaggat gttgacgggg gcacatctgt tgcggtttcg gaaaaggagg 2220

agggtatggc tgacgtcagt gggcaagtaa gtgacgatga atattcacaa gaagatgctt 2280

taaaaatgct caaggccata aagtccttag acgagtccta cagaagaaaa ccttcgtctt 2340

ctgagtctca tgcctcaaaa cctagtttga tagacaggat caggtataga ggttataaga 2400

gtgtaaatgt agaagaagcg tga 2423

<210> 84

<211> 2493

<212> DNA

<213> artificial sequence

<220>

<223> beta 30 sheet single amino acid SNP at NC_001664.4, c62129-59637

Human beta-herpesvirus 6A, variant A DNA, virosome genome, strain

U1102 glycoprotein gB U39 gene 1730a-c E678A

<400> 84

atgagcaaga tggcagtatt attcctggct gtctttttga tgaatagtgt tttaatgata 60

tattgtgatc cggatcatta tatcagagcg ggctataatc acaaatatcc ttttcggatt 120

tgttcgattg ccaaaggcac ggatttaatg cggttcgaca gagatatttc gtgctcgccg 180

tataagtcta atgcaaagat gtcggagggt tttttcatca tttacaaaac aaatatcgag 240

acctacactt ttccagtgag aacgtataaa aaagagttga cgttccaaag tagttaccgt 300

gatgtgggtg tggtttattt tctggatcgg acggtgatgg gtttggccat gccggtgtac 360

gaagcaaatt tagttaattc tcatgcgcag tgttattccg ccgtagcgat gaaacgaccc 420

gatggtacgg tgtttagtgc ctttcatgag gataataata aaaacaatac tctaaattta 480

tttcctctga atttcaaatc tataactaat aaaagattta tcactacgaa agaaccctac 540

tttgcaaggg gtcctttgtg gctatattct acatcaacgt ctctcaattg tattgtgacg 600

gaggctacgg ctaaggcgaa atacccgttt agttactttg ctttgacgac tggcgaaatc 660

gtggaagggt ctccgttctt caacggttca aacggtaaac attttgcaga gccgttagaa 720

aaattgacaa tcttggaaaa ctatactatg atagaagatc taatgaatgg tatgaatggg 780

gccactacgt tagtgaggaa aatcgctttt ctcgagaaag cggatacttt gttttcttgg 840

gaaatcaagg aagagaatga atcggtgtgt atgctaaagc actggaccac ggtgactcac 900

gggcttcgag cggagacgaa tgagacctat cactttatct ctaaggagtt gacagccgct 960

ttcgtcgccc ccaaggagtc cttaaatctt accgatccga aacaaacgtg tattaagaat 1020

gaatttgaaa aaataattaa tgaagtctat atgtcagatt ataatgatac atatagcatg 1080

aatggtagtt atcaaatttt taagactacg ggagatttga ttttgatttg gcaacctctt 1140

gtgcaaaaat ctcttatgtt tcttgagcag ggttcggaaa aaatacgtag gaggcgagat 1200

gtgggggatg ttaagtctag acatgatatt ctttatgtgc aattacagta tctttatgat 1260

actttgaaag attatatcaa tgatgcattg gggaatttgg cagaatcttg gtgtctcgat 1320

caaaagcgaa cgataacgat gttgcacgaa cttagtaaga ttagtccgtc gagtatcgtg 1380

tctgaggttt acggtcgtcc gatatctgca cagttgcatg gtgacgtgtt agctatctcg 1440

aaatgcatag aggttaatca gtcatccgtt cagcttcata agagtatgcg ggtcgtcgat 1500

gcaaagggag taaggagtga aacgatgtgt tataatcggc ccttggtgac gtttagtttt 1560

gtgaactcga cgcctgaggt tgtccctggc cagctagggt tagataatga aattctgttg 1620

ggtgatcata ggacagagga atgtgaaata cctagtacaa agatcttttt atctggaaat 1680

catgcgcacg tgtataccga ttatacgcat acgaattcga cgcccatagc agacattgag 1740

gtattggatg cttttattag actaaaaatc gatcctcttg aaaatgccga ttttaaagta 1800

ctcgatttat attcgccgga cgaattgagt agagcaaacg ttttcgatct agagaatatt 1860

cttcgtgaat ataactcata taagagcgca ctatatacta tagaagctaa aattgctacg 1920

aatacacctt cgtatgttaa tgggattaat tcttttttac aagggcttgg ggctataggc 1980

actggattgg gctcggttat aagtgttacg gcaggagcgc ttggggatat tgtgggtgga 2040

gtggtgtctt ttctaaaaaa tccattcggg ggtggtctca tgttgatttt agcgatagta 2100

gttgttgtga taataattgt ggttttcgtt agacaaagac atgtgcttag taagcctatt 2160

gacatgatgt ttccttatgc caccaatccg gtgactactg tgtccagtgt tacggggacc 2220

actgtcgtca agacacctag tgttaaggat gttgacgggg gcacatctgt tgcggtttcg 2280

gaaaaggagg agggtatggc tgacgtcagt gggcaagtaa gtgacgatga atattcacaa 2340

gaagatgctt taaaaatgct caaggccata aagtccttag acgagtccta cagaagaaaa 2400

ccttcgtctt ctgagtctca tgcctcaaaa cctagtttga tagacaggat caggtataga 2460

ggttataaga gtgtaaatgt agaagaagcg tga 2493

<210> 85

<211> 2493

<212> DNA

<213> artificial sequence

<220>

<223> beta 30 sheet double amino acid SNP, at NC-000898.1:c63200-60708

Human herpesvirus 6B, strain Z29 genome gB U39 gene 1708ca-gc

1730a-c H670A E677A

<400> 85

atgagcaaga tgagagtatt attcctggct gtctttttga tgaatagtgt tttaatgata 60

tattgcgatt cggatgatta tatcagagcg ggctataatc acaaatatcc ttttcggatt 120

tgttcgattg ccaaaggcac tgatttgatg cggttcgaca gagatatttc gtgttcgcca 180

tataagtcta atgcaaagat gtcggagggt tttttcatca tttacaaaac aaatatcgag 240

acctacactt ttccagtgag aacatataaa aacgagctga cgttcccaac cagttaccgt 300

gatgtgggtg tggtttattt tctggatcgg acggtgatgg gtttggccat gccggtgtac 360

gaagcaaatt tagttaattc tcgtgcgcag tgttattcag ccgtagcgat aaaacgaccc 420

gatggtacgg tgtttagtgc ctatcatgag gataataata aaaacgaaac tctagaatta 480

tttcctctga atttcaagtc tgttactaat aaaagattta tcactacgaa agaaccctac 540

tttgcaaggg gtcctttgtg gctctattct acatcgacgt ctctcaattg tattgtgacg 600

gaggctacgg ctaaggcgaa atatccgttt agttactttg ctttgacgac tggtgaaatc 660

gtggaagggt ctccgttctt cgacggttca aacggtaaac attttgcaga gccgttagaa 720

aaattgacaa tcttggaaaa ctatactatg atagaagatc taatgaatgg tatgaatggg 780

gctactacgt tagtaaggaa gatcgctttt ctggagaaag gggatacttt gttttcttgg 840

gaaatcaagg aagagaatga atcggtgtgt atgctaaagc actggactac ggtgactcac 900

gggcttcgag cggagacgga tgagacttat cactttattt ctaaggagtt gacagccgct 960

ttcgtcgcct ccaaggagtc tttaaatctt accgatccca aacaaacgtg tattaagaat 1020

gaatttgaga agataattac agatgtctat atgtcagatt ataatgatgc atacagcatg 1080

aacggtagtt atcaaatttt taagactacg ggagatctga ttttgatttg gcagcctctt 1140

gtgcaaaaat ctcttatggt tcttgagcag ggttcagtaa acttacgtag gaggcgagat 1200

ttggtggatg tcaagtctag acatgatatt ctttatgtgc aattacagta cctctatgat 1260

actttgaaag attatatcaa cgatgccttg gggaatttgg cagaatcttg gtgcctcgat 1320

caaaaacgaa cgataacgat gttgcacgaa cttagtaaga tcagtccatc gagtatcgtg 1380

tctgaggttt acggtcgtcc gatatctgca cagttgcatg gtgatgtgtt agctatctcg 1440

aaatgcatag aagttaatca atcatccgtt cagctttata agagtatgcg ggtcgtcgat 1500

gcgaagggag taaggagtga aacgatgtgt tataatcggc ccttggtgac gtttagcttt 1560

gtgaactcca cgcctgaggt tgtccttggt cagctagggt tagataatga gattctgttg 1620

ggtgatcata ggacagagga atgtgagata cctagtacaa agatatttct atctggaaat 1680

catgcacacg tgtataccga ttatacggct acgaattcga cgcccatagc agacattgag 1740

gtattggatg cttttattag actaaagatc gaccctctcg aaaatgctga ttttaaacta 1800

cttgatttat attcgccgga cgaattgagt agagcaaacg ttttcgattt agagaatatt 1860

cttcgtgaat ataactcata taagagcgca ctatatacta tagaagctaa aattgctact 1920

aatacgccgt cgtatgtcaa tgggattaat tcttttttac aagggcttgg ggctataggc 1980

actggattgg gctcggttat aagtgttacg gcaggagcac ttggggatat tgtgggtgga 2040

gtggtgtctt ttttaaaaaa tccattcggg ggtggtctca tgttgatttt agcgatagta 2100

gttgtcgtta taataattgt ggttttcgtt agacaaaaac atgtgcttag taagcctatt 2160

gacatgatgt ttccttatgc caccaatccg gtgactactg tgtccagtgt tacggggacc 2220

actgtcgtca agacgcctag tgttaaagat gctgacgggg gcacatctgt tgcggtttcg 2280

gaaaaagagg agggtatggc tgacgtcagt ggacaaataa gtggtgatga atattcacaa 2340

gaagatgctt taaaaatgct caaggccata aagtctttag acgagtccta cagaagaaaa 2400

ccttcgtctt ctgagtctca tgcctcaaaa cctagtttga tagacaggat caggtataga 2460

ggttataaga gtgtaaatgt agaagaagcg tga 2493

<210> 86

<211> 2493

<212> DNA

<213> artificial sequence

<220>

<223> beta 30 sheet single amino acid SNP at gBNC-000898.1:c63200-60708

Human herpesvirus 6B, strain Z29 genome gB U39 gene, returning CA to-

1730a-c E677A

<400> 86

atgagcaaga tgagagtatt attcctggct gtctttttga tgaatagtgt tttaatgata 60

tattgcgatt cggatgatta tatcagagcg ggctataatc acaaatatcc ttttcggatt 120

tgttcgattg ccaaaggcac tgatttgatg cggttcgaca gagatatttc gtgttcgcca 180

tataagtcta atgcaaagat gtcggagggt tttttcatca tttacaaaac aaatatcgag 240

acctacactt ttccagtgag aacatataaa aacgagctga cgttcccaac cagttaccgt 300

gatgtgggtg tggtttattt tctggatcgg acggtgatgg gtttggccat gccggtgtac 360

gaagcaaatt tagttaattc tcgtgcgcag tgttattcag ccgtagcgat aaaacgaccc 420

gatggtacgg tgtttagtgc ctatcatgag gataataata aaaacgaaac tctagaatta 480

tttcctctga atttcaagtc tgttactaat aaaagattta tcactacgaa agaaccctac 540

tttgcaaggg gtcctttgtg gctctattct acatcgacgt ctctcaattg tattgtgacg 600

gaggctacgg ctaaggcgaa atatccgttt agttactttg ctttgacgac tggtgaaatc 660

gtggaagggt ctccgttctt cgacggttca aacggtaaac attttgcaga gccgttagaa 720

aaattgacaa tcttggaaaa ctatactatg atagaagatc taatgaatgg tatgaatggg 780

gctactacgt tagtaaggaa gatcgctttt ctggagaaag gggatacttt gttttcttgg 840

gaaatcaagg aagagaatga atcggtgtgt atgctaaagc actggactac ggtgactcac 900

gggcttcgag cggagacgga tgagacttat cactttattt ctaaggagtt gacagccgct 960

ttcgtcgcct ccaaggagtc tttaaatctt accgatccca aacaaacgtg tattaagaat 1020

gaatttgaga agataattac agatgtctat atgtcagatt ataatgatgc atacagcatg 1080

aacggtagtt atcaaatttt taagactacg ggagatctga ttttgatttg gcagcctctt 1140

gtgcaaaaat ctcttatggt tcttgagcag ggttcagtaa acttacgtag gaggcgagat 1200

ttggtggatg tcaagtctag acatgatatt ctttatgtgc aattacagta cctctatgat 1260

actttgaaag attatatcaa cgatgccttg gggaatttgg cagaatcttg gtgcctcgat 1320

caaaaacgaa cgataacgat gttgcacgaa cttagtaaga tcagtccatc gagtatcgtg 1380

tctgaggttt acggtcgtcc gatatctgca cagttgcatg gtgatgtgtt agctatctcg 1440

aaatgcatag aagttaatca atcatccgtt cagctttata agagtatgcg ggtcgtcgat 1500

gcgaagggag taaggagtga aacgatgtgt tataatcggc ccttggtgac gtttagcttt 1560

gtgaactcca cgcctgaggt tgtccttggt cagctagggt tagataatga gattctgttg 1620

ggtgatcata ggacagagga atgtgagata cctagtacaa agatatttct atctggaaat 1680

catgcacacg tgtataccga ttatacgcat acgaattcga cgcccatagc agacattgag 1740

gtattggatg cttttattag actaaagatc gaccctctcg aaaatgctga ttttaaacta 1800

cttgatttat attcgccgga cgaattgagt agagcaaacg ttttcgattt agagaatatt 1860

cttcgtgaat ataactcata taagagcgca ctatatacta tagaagctaa aattgctact 1920

aatacgccgt cgtatgtcaa tgggattaat tcttttttac aagggcttgg ggctataggc 1980

actggattgg gctcggttat aagtgttacg gcaggagcac ttggggatat tgtgggtgga 2040

gtggtgtctt ttttaaaaaa tccattcggg ggtggtctca tgttgatttt agcgatagta 2100

gttgtcgtta taataattgt ggttttcgtt agacaaaaac atgtgcttag taagcctatt 2160

gacatgatgt ttccttatgc caccaatccg gtgactactg tgtccagtgt tacggggacc 2220

actgtcgtca agacgcctag tgttaaagat gctgacgggg gcacatctgt tgcggtttcg 2280

gaaaaagagg agggtatggc tgacgtcagt ggacaaataa gtggtgatga atattcacaa 2340

gaagatgctt taaaaatgct caaggccata aagtctttag acgagtccta cagaagaaaa 2400

ccttcgtctt ctgagtctca tgcctcaaaa cctagtttga tagacaggat caggtataga 2460

ggttataaga gtgtaaatgt agaagaagcg tga 2493

<210> 87

<211> 2469

<212> DNA

<213> artificial sequence

<220>

<223> beta 30 sheet double amino acid SNP at NC_001716.2:c61093-58625

Human herpesvirus 7 genome, glycoprotein gB U39 1693ta-gc 1718a-c

Y665A E673A

<400> 87

atgaaaattc tattcctgag tgtttttata acttttagct tacagctatc tctacaaaca 60

gaagctgact ttgtcatgac tggacacaat cagcatttac catttcgaat ttgttcaatt 120

gccaccggga cagatttagt gcgttttgac agggaggttt cttgcgcgtc ttacggctct 180

aacattaaaa ctaccgaagg tattttgata atttacaaaa caaagattga agcacacacg 240

ttttctgtca gaacttttaa aaaagaactt acatttcaaa caacatatcg cgatgttggc 300

actgtgtatt tcttagatcg aactgttaca actttgccaa tgccaattga agaagtgcac 360

atggtaaaca ccgaggcgcg ttgtttgtcc tctatctctg taaaacgttc ggaggaagag 420

gagtatgttg catatcataa agatgaatat gtgaataaaa cgttggattt gattccgtta 480

aattttaaat ctgatactgt cagaagatat ataactacta aagaaccatt tttaagaaat 540

ggtcccctct ggttctattc aacatctaca tcgataaatt gcatagttac agactgcatt 600

gcaaagacta aatatccttt tgattttttt gctttatcaa caggggaaac cgtggaaggg 660

tcaccgtttt ataatggtat taattctaaa acatttaatg aaccaacgga aaaaattttg 720

tttagaaata attatactat gctgaaaacg tttgatgatg gatcaaaagg aaattttgtg 780

acgttaacta aaatggcttt tctggaaaag ggaaatacta ttttttcatg ggaagtgcag 840

aatgaagagt cttccatttg tttgttaaag cattggatga caatcccaca cgctttacgg 900

gcagaaaatg ctaacagttt tcactttatt gcgcaggaac taactgcttc ttttgtcaca 960

ggaaaaagta attatacgct ttctgattca aaatataatt gtattaacag caattatact 1020

tcaattttgg atgagattta ccaaacgcaa tacaacaatt cgcatgacaa aaatggtagt 1080

tatgaaattt ttaaaactga gggagattta attctgattt ggcaaccgtt aatacaacgg 1140

aaattaacgg ttttggaaaa tttttctaat gcttctagaa aaaggaggaa gagggaatta 1200

gagactaaca aagacatcgt atatgttcaa ctacaatacc tatacgacac tctgaaagat 1260

tacattaaca cagcactagg taagcttgct gaagcctggt gtttagatca aaaacgcact 1320

atcacagtgt tgcacgagct tagtaaaata agtccttctg gaatcatttc agcagtgtac 1380

ggtaaaccca tgtccgctaa attaattggt gatgtattag cagtctcaaa gtgcattgaa 1440

gtcaaccaga cttctgttca gctacataaa agtatgagat tgacaaaaga ttcaagttac 1500

gatgctctaa gatgttattc tcggccattg ttaacatatt catttgcaaa ttcttcgaag 1560

gaaacttatt taggacaact tggtttagac aatgagatat tactgggaaa tcacagaaca 1620

gaagaatgtg aacaatctaa cacgaaaatt tttttgtctg gtaaattcgc tcatattttt 1680

aaagactata cggccgttaa ttctagtttg ataacagcaa tagaagcttt agatgcgttt 1740

gttgacttaa acatagatcc tttagaaaat gcagatttta cattattgga attgtataca 1800

aaagatgaac tgagcaaagc gaacgttttt gatttggaaa ccattcttag agaatacaat 1860

tcttacaaaa gtgcgctaca ccatatagaa acaaaaattg caactgttac tccaacatat 1920

ataggaggga ttgacacatt tttcaaaggt cttggcgctc ttggtcttgg tttgggggct 1980

gtgctgggtg taacggctgg tgctttggga gatgtggtga atggagtttt ctcttttctt 2040

aaaaatccat ttggtggagc actaactatc ttactaactt tgggagtgat tggcttagtt 2100

attttcttat ttttaagaca taaacgatta gcacaaacac cgattgatat tttatttcct 2160

tatacatcaa aatcaacaaa ttcggtactt caagcaacgc aatcagttca agcgcaagtg 2220

aaagaacctt tagattcatc tccgccttat ttaaaaacta acaaagacac agaaccgcaa 2280

ggtgatgaca taacacacac taatgaatat tcacaagtgg aagctttaaa aatgttgaaa 2340

gctattaaat tattagatga gtcatataaa aaagcggaaa tcgctgaggc aaaaaaatca 2400

cagagaccaa gcctacttga aaggattcaa tacaggggct atcagaaact ttcaacagaa 2460

gaactgtga 2469

<210> 88

<211> 2469

<212> DNA

<213> artificial sequence

<220>

<223> beta 30 sheet single amino acid SNP at NC_001716.2:c61093-58625

Human herpesvirus 7 genome, glycoprotein gB U39 ta-gc a-c E673A

<400> 88

atgaaaattc tattcctgag tgtttttata acttttagct tacagctatc tctacaaaca 60

gaagctgact ttgtcatgac tggacacaat cagcatttac catttcgaat ttgttcaatt 120

gccaccggga cagatttagt gcgttttgac agggaggttt cttgcgcgtc ttacggctct 180

aacattaaaa ctaccgaagg tattttgata atttacaaaa caaagattga agcacacacg 240

ttttctgtca gaacttttaa aaaagaactt acatttcaaa caacatatcg cgatgttggc 300

actgtgtatt tcttagatcg aactgttaca actttgccaa tgccaattga agaagtgcac 360

atggtaaaca ccgaggcgcg ttgtttgtcc tctatctctg taaaacgttc ggaggaagag 420

gagtatgttg catatcataa agatgaatat gtgaataaaa cgttggattt gattccgtta 480

aattttaaat ctgatactgt cagaagatat ataactacta aagaaccatt tttaagaaat 540

ggtcccctct ggttctattc aacatctaca tcgataaatt gcatagttac agactgcatt 600

gcaaagacta aatatccttt tgattttttt gctttatcaa caggggaaac cgtggaaggg 660

tcaccgtttt ataatggtat taattctaaa acatttaatg aaccaacgga aaaaattttg 720

tttagaaata attatactat gctgaaaacg tttgatgatg gatcaaaagg aaattttgtg 780

acgttaacta aaatggcttt tctggaaaag ggaaatacta ttttttcatg ggaagtgcag 840

aatgaagagt cttccatttg tttgttaaag cattggatga caatcccaca cgctttacgg 900

gcagaaaatg ctaacagttt tcactttatt gcgcaggaac taactgcttc ttttgtcaca 960

ggaaaaagta attatacgct ttctgattca aaatataatt gtattaacag caattatact 1020

tcaattttgg atgagattta ccaaacgcaa tacaacaatt cgcatgacaa aaatggtagt 1080

tatgaaattt ttaaaactga gggagattta attctgattt ggcaaccgtt aatacaacgg 1140

aaattaacgg ttttggaaaa tttttctaat gcttctagaa aaaggaggaa gagggaatta 1200

gagactaaca aagacatcgt atatgttcaa ctacaatacc tatacgacac tctgaaagat 1260

tacattaaca cagcactagg taagcttgct gaagcctggt gtttagatca aaaacgcact 1320

atcacagtgt tgcacgagct tagtaaaata agtccttctg gaatcatttc agcagtgtac 1380

ggtaaaccca tgtccgctaa attaattggt gatgtattag cagtctcaaa gtgcattgaa 1440

gtcaaccaga cttctgttca gctacataaa agtatgagat tgacaaaaga ttcaagttac 1500

gatgctctaa gatgttattc tcggccattg ttaacatatt catttgcaaa ttcttcgaag 1560

gaaacttatt taggacaact tggtttagac aatgagatat tactgggaaa tcacagaaca 1620

gaagaatgtg aacaatctaa cacgaaaatt tttttgtctg gtaaattcgc tcatattttt 1680

aaagactata cgtacgttaa ttctagtttg ataacagcaa tagaagcttt agatgcgttt 1740

gttgacttaa acatagatcc tttagaaaat gcagatttta cattattgga attgtataca 1800

aaagatgaac tgagcaaagc gaacgttttt gatttggaaa ccattcttag agaatacaat 1860

tcttacaaaa gtgcgctaca ccatatagaa acaaaaattg caactgttac tccaacatat 1920

ataggaggga ttgacacatt tttcaaaggt cttggcgctc ttggtcttgg tttgggggct 1980

gtgctgggtg taacggctgg tgctttggga gatgtggtga atggagtttt ctcttttctt 2040

aaaaatccat ttggtggagc actaactatc ttactaactt tgggagtgat tggcttagtt 2100

attttcttat ttttaagaca taaacgatta gcacaaacac cgattgatat tttatttcct 2160

tatacatcaa aatcaacaaa ttcggtactt caagcaacgc aatcagttca agcgcaagtg 2220

aaagaacctt tagattcatc tccgccttat ttaaaaacta acaaagacac agaaccgcaa 2280

ggtgatgaca taacacacac taatgaatat tcacaagtgg aagctttaaa aatgttgaaa 2340

gctattaaat tattagatga gtcatataaa aaagcggaaa tcgctgaggc aaaaaaatca 2400

cagagaccaa gcctacttga aaggattcaa tacaggggct atcagaaact ttcaacagaa 2460

gaactgtga 2469

<210> 89

<211> 2538

<212> DNA

<213> artificial sequence

<220>

<223> beta 30 sheet double amino acid SNP in NC_009333.1:8665-11202

Human herpesvirus 8 GK18 genome glycoprotein gB gene ORF8

1825ta-gc 1840aa-gc Y608A N613A

<400> 89

atgactccca ggtctagatt ggccaccctg gggactgtca tcctgttggt ctgcttttgc 60

gcaggcgcgg cgcactcgag gggtgacacc tttcagacgt ccagttcccc cacaccccca 120

ggatcttcct ctaaggcccc caccaaacct ggtgaggaag catctggtcc taagagtgtg 180

gacttttacc agttcagagt gtgtagtgca tcgatcaccg gggagctttt tcggttcaac 240

ctggagcaga cgtgcccaga caccaaagac aagtaccacc aagaaggaat tttactggtg 300

tacaaaaaaa acatagtgcc tcatatcttt aaggtgcggc gctataggaa aattgccacc 360

tctgtcacgg tctacagggg cttgacagag tccgccatca ccaacaagta tgaactcccg 420

agacccgtgc cactctatga gataagccac atggacagca cctatcagtg ctttagttcc 480

atgaaggtaa atgtcaacgg ggtagaaaac acatttactg acagagacga tgttaacacc 540

acagtattcc tccaaccagt agaggggctt acggataaca ttcaaaggta ctttagccag 600

ccggtcatct acgcggaacc cggctggttt cccggcatat acagagttag gaccaccgtc 660

aattgcgaga tagtggacat gatagccagg tctgctgaac catacaatta ctttgtcacg 720

tcactgggtg acacggtgga agtctcccct ttttgctata acgaatcctc atgcagcaca 780

acccccagca acaaaaatgg ccttagcgtc caagtagttc tcaaccacac tgtggtcacg 840

tactctgaca gaggaaccag tcccactccc caaaacagga tctttgtgga aacgggagcg 900

tacacgcttt cgtgggcctc cgagagcaag accacggccg tgtgtccgct ggcactgtgg 960

aaaaccttcc cgcgctccat ccagactacc cacgaggaca gcttccactt tgtggccaac 1020

gagatcacgg ccaccttcac ggctcctcta acgccagtgg ccaactttac cgacacgtac 1080

tcttgtctga cctcggatat caacaccacg ctaaacgcca gcaaggccaa actggcgagc 1140

actcacgtcc ctaacgggac ggtccagtac ttccacacaa caggcggact ctatttggtc 1200

tggcagccca tgtccgcgat taacctgact cacgctcagg gcgacagcgg gaaccccacg 1260

tcatcgccgc ccccctccgc atcccccatg accacctctg ccagccgcag aaagagacgg 1320

tcagccagta ccgctgctgc cggcggcggg gggtccacgg acaacctgtc ttacacgcag 1380

ctgcagtttg cctacgacaa actgcgggat ggcattaatc aggtgttaga agaactctcc 1440

agggcatggt gtcgcgagca ggtcagggac aacctaatgt ggtacgagct cagtaaaatc 1500

aaccccacca gcgttatgac agccatctac ggtcgacctg tatccgccaa gttcgtagga 1560

gacgccattt ccgtgaccga gtgcattaac gtggaccaga gctccgtaaa catccacaag 1620

agcctcagaa ccaatagtaa ggacgtgtgt tacgcgcgcc ccctggtgac gtttaagttt 1680

ttgaacagtt ccaacctatt caccggccag ctgggcgcgc gcaatgagat aatactgacc 1740

aacaaccagg tggaaacctg caaagacacc tgcgaacact acttcatcac ccgcaacgag 1800

actctggtgt ataaggacta cgcggccctg cgtactatag ccaccactga catatccacc 1860

ctgaacactt ttatcgccct gaatctatcc tttattcaaa acatagactt caaggccatc 1920

gagctgtaca gcagtgcaga gaaacgactc gcgagtagcg tgtttgacct ggagacgatg 1980

ttcagggagt acaactacta cacacatcgt ctcgcgggtt tgcgcgagga tctggacaac 2040

accatagata tgaacaagga gcgcttcgta agggacttgt cggagatagt ggcggacctg 2100

ggtggcatcg gaaaaacggt ggtgaacgtg gccagcagcg tggtcactct atgtggctca 2160

ttggttaccg gattcataaa ttttattaaa caccccctag gtggcatgct gatgatcatt 2220

atcgttatag caatcatcct gatcattttt atgctcagtc gccgcaccaa taccatagcc 2280

caggcgccgg tgaagatgat ctaccccgac gtagatcgca gggcacctcc tagcggcgga 2340

gccccaacac gggaggaaat caaaaacatc ctgctgggaa tgcaccagct acaacaagag 2400

gagaggcaga aggcggatga tctgaaaaaa agtacaccct cggtgtttca gcgtaccgca 2460

aacggccttc gtcagcgtct gagaggatat aaacctctga ctcaatcgct agacatcagt 2520

ccggaaacgg gggagtga 2538

<210> 90

<211> 2538

<212> DNA

<213> artificial sequence

<220>

<223> beta 30 sheet single amino acid SNP at NC_009333.1:8665-11202

Human herpesvirus 8 GK18 genome gB gene ORF8 1840aa-gc

N613A

<400> 90

atgactccca ggtctagatt ggccaccctg gggactgtca tcctgttggt ctgcttttgc 60

gcaggcgcgg cgcactcgag gggtgacacc tttcagacgt ccagttcccc cacaccccca 120

ggatcttcct ctaaggcccc caccaaacct ggtgaggaag catctggtcc taagagtgtg 180

gacttttacc agttcagagt gtgtagtgca tcgatcaccg gggagctttt tcggttcaac 240

ctggagcaga cgtgcccaga caccaaagac aagtaccacc aagaaggaat tttactggtg 300

tacaaaaaaa acatagtgcc tcatatcttt aaggtgcggc gctataggaa aattgccacc 360

tctgtcacgg tctacagggg cttgacagag tccgccatca ccaacaagta tgaactcccg 420

agacccgtgc cactctatga gataagccac atggacagca cctatcagtg ctttagttcc 480

atgaaggtaa atgtcaacgg ggtagaaaac acatttactg acagagacga tgttaacacc 540

acagtattcc tccaaccagt agaggggctt acggataaca ttcaaaggta ctttagccag 600

ccggtcatct acgcggaacc cggctggttt cccggcatat acagagttag gaccaccgtc 660

aattgcgaga tagtggacat gatagccagg tctgctgaac catacaatta ctttgtcacg 720

tcactgggtg acacggtgga agtctcccct ttttgctata acgaatcctc atgcagcaca 780

acccccagca acaaaaatgg ccttagcgtc caagtagttc tcaaccacac tgtggtcacg 840

tactctgaca gaggaaccag tcccactccc caaaacagga tctttgtgga aacgggagcg 900

tacacgcttt cgtgggcctc cgagagcaag accacggccg tgtgtccgct ggcactgtgg 960

aaaaccttcc cgcgctccat ccagactacc cacgaggaca gcttccactt tgtggccaac 1020

gagatcacgg ccaccttcac ggctcctcta acgccagtgg ccaactttac cgacacgtac 1080

tcttgtctga cctcggatat caacaccacg ctaaacgcca gcaaggccaa actggcgagc 1140

actcacgtcc ctaacgggac ggtccagtac ttccacacaa caggcggact ctatttggtc 1200

tggcagccca tgtccgcgat taacctgact cacgctcagg gcgacagcgg gaaccccacg 1260

tcatcgccgc ccccctccgc atcccccatg accacctctg ccagccgcag aaagagacgg 1320

tcagccagta ccgctgctgc cggcggcggg gggtccacgg acaacctgtc ttacacgcag 1380

ctgcagtttg cctacgacaa actgcgggat ggcattaatc aggtgttaga agaactctcc 1440

agggcatggt gtcgcgagca ggtcagggac aacctaatgt ggtacgagct cagtaaaatc 1500

aaccccacca gcgttatgac agccatctac ggtcgacctg tatccgccaa gttcgtagga 1560

gacgccattt ccgtgaccga gtgcattaac gtggaccaga gctccgtaaa catccacaag 1620

agcctcagaa ccaatagtaa ggacgtgtgt tacgcgcgcc ccctggtgac gtttaagttt 1680

ttgaacagtt ccaacctatt caccggccag ctgggcgcgc gcaatgagat aatactgacc 1740

aacaaccagg tggaaacctg caaagacacc tgcgaacact acttcatcac ccgcaacgag 1800

actctggtgt ataaggacta cgcgtacctg cgtactatag ccaccactga catatccacc 1860

ctgaacactt ttatcgccct gaatctatcc tttattcaaa acatagactt caaggccatc 1920

gagctgtaca gcagtgcaga gaaacgactc gcgagtagcg tgtttgacct ggagacgatg 1980

ttcagggagt acaactacta cacacatcgt ctcgcgggtt tgcgcgagga tctggacaac 2040

accatagata tgaacaagga gcgcttcgta agggacttgt cggagatagt ggcggacctg 2100

ggtggcatcg gaaaaacggt ggtgaacgtg gccagcagcg tggtcactct atgtggctca 2160

ttggttaccg gattcataaa ttttattaaa caccccctag gtggcatgct gatgatcatt 2220

atcgttatag caatcatcct gatcattttt atgctcagtc gccgcaccaa taccatagcc 2280

caggcgccgg tgaagatgat ctaccccgac gtagatcgca gggcacctcc tagcggcgga 2340

gccccaacac gggaggaaat caaaaacatc ctgctgggaa tgcaccagct acaacaagag 2400

gagaggcaga aggcggatga tctgaaaaaa agtacaccct cggtgtttca gcgtaccgca 2460

aacggccttc gtcagcgtct gagaggatat aaacctctga ctcaatcgct agacatcagt 2520

ccggaaacgg gggagtga 2538

<210> 91

<211> 2715

<212> DNA

<213> artificial sequence

<220>

<223> Domain I SNP A799G gB1 HSV1 Strain 17

<400> 91

atgcgccagg gcgcccccgc gcgggggcgc cggtggttcg tcgtatgggc gctcttgggg 60

ttgacgctgg gggtcctggt ggcgtcggcg gctccgagtt cccccggcac gcctggggtc 120

gcggccgcga cccaggcggc gaacgggggc cctgccactc cggcgccgcc cgcccctggc 180

gcccccccaa cgggggaccc gaaaccgaag aagaacaaaa aaccgaaacc cccaaagccg 240

ccgcgccccg ccggcgacaa cgcgaccgtc gccgcgggcc acgccaccct gcgcgagcac 300

ctgcgggaca tcaaggcgga gaacaccgat gcaaactttt acgtgtgccc accccccacg 360

ggcgccacgg tggtgcagtt cgagcagccg cgccgctgcc cgacccggcc cgagggtcag 420

aactacacgg agggcatcgc ggtggtcttc aaggagaaca tcgccccgta caagttcaag 480

gccaccatgt actacaaaga cgtcaccgtt tcgcaggtgt ggttcggcca ccgctactcc 540

cagtttatgg ggatctttga ggaccgcgcc cccgtcccct tcgaggaggt gatcgacaag 600

atcaacgcca agggggtctg tcggtccacg gccaagtacg tgcgcaacaa cctggagacc 660

accgcgtttc accgggacga ccacgagacc gacatggagc tgaaaccggc caacgccgcg 720

acccgcacga gccggggctg gcacaccacc gacctcaagt acaacccctc gcgggtggag 780

gcgttccacc ggtacggggc gacggtaaac tgcatcgtcg aggaggtgga cgcgcgctcg 840

gtgtacccgt acgacgagtt tgtgttggcg actggcgact ttgtgtacat gtccccgttt 900

tacggctacc gggaggggtc gcacaccgaa cacaccagct acgccgccga ccgcttcaag 960

caggtcgacg gcttctacgc gcgcgacctc accaccaagg cccgggccac ggcgccgacc 1020

acccggaacc tgctcacgac ccccaagttc accgtggcct gggactgggt gccaaagcgc 1080

ccgtcggtct gcaccatgac caagtggcag gaggtggacg agatgctgcg ctccgagtac 1140

ggcggctcct tccgattctc ttccgacgcc atatccacca ccttcaccac caacctgacc 1200

gagtacccgc tctcgcgcgt ggacctgggg gactgcatcg gcaaggacgc ccgcgacgcc 1260

atggaccgca tcttcgcccg caggtacaac gcgacgcaca tcaaggtggg ccagccgcag 1320

tactacctgg ccaatggggg ctttctgatc gcgtaccagc cccttctcag caacacgctc 1380

gcggagctgt acgtgcggga acacctccgc gagcagagcc gcaagccccc aaaccccacg 1440

cccccgccgc ccggggccag cgccaacgcg tccgtggagc gcatcaagac cacctcctcc 1500

atcgagttcg ccaggctgca gtttacgtac aaccacatac agcgccatgt caacgatatg 1560

ttgggccgcg ttgccatcgc gtggtgcgag ctgcagaatc acgagctgac cctgtggaac 1620

gaggcccgca agctgaaccc caacgccatc gcctcggcca ccgtgggccg gcgggtgagc 1680

gcgcggatgc tcggcgacgt gatggccgtc tccacgtgcg tgccggtcgc cgcggacaac 1740

gtgatcgtcc aaaactcgat gcgcatcagc tcgcggcccg gggcctgcta cagccgcccc 1800

ctggtcagct ttcggtacga agaccagggc ccgttggtcg aggggcagct gggggagaac 1860

aacgagctgc ggctgacgcg cgatgcgatc gagccgtgca ccgtgggaca ccggcgctac 1920

ttcaccttcg gtgggggcta cgtgtacttc gaggagtacg cgtactccca ccagctgagc 1980

cgcgccgaca tcaccaccgt cagcaccttc atcgacctca acatcaccat gctggaggat 2040

cacgagtttg tccccctgga ggtgtacacc cgccacgaga tcaaggacag cggcctgctg 2100

gactacacgg aggtccagcg ccgcaaccag ctgcacgacc tgcgcttcgc cgacatcgac 2160

acggtcatcc acgccgacgc caacgccgcc atgtttgcgg gcctgggcgc gttcttcgag 2220

gggatgggcg acctggggcg cgcggtcggc aaggtggtga tgggcatcgt gggcggcgtg 2280

gtatcggccg tgtcgggcgt gtcctccttc atgtccaacc cctttggggc gctggccgtg 2340

ggtctgttgg tcctggccgg cctggcggcg gccttcttcg cctttcgcta cgtcatgcgg 2400

ctgcagagca accccatgaa ggccctgtac ccgctaacca ccaaggagct caagaacccc 2460

accaacccgg acgcgtccgg ggagggcgag gagggcggcg actttgacga ggccaagcta 2520

gccgaggccc gggagatgat acggtacatg gccctggtgt ctgccatgga gcgcacggaa 2580

cacaaggcca agaagaaggg cacgagcgcg ctgctcagcg ccaaggtcac cgacatggtc 2640

atgcgcaagc gccgcaacac caactacacc caagttccca acaaagacgg tgacgccgac 2700

gaggacgacc tgtga 2715

<210> 92

<211> 2796

<212> DNA

<213> artificial sequence

<220>

<223> Domain I SNP A817G gB3 VZV Strain Dumas

<400> 92

atgtcccctt gtggctatta ttcaaagtgg agaaacaggg atcgaccaga ataccgtcgt 60

aatctacgat tcagacgttt tttctcttct atacacccta atgcagcggc tggctccgga 120

ttcaacggac ccggcgtttt cataacctcc gttacggggg tgtggttatg ctttttatgc 180

atattttcta tgtttgttac ggcggttgtg tcggtctctc caagctcgtt ttatgagagt 240

ttacaagtag agcccacaca atcagaagat ataacccggt ctgctcatct gggcgatggt 300

gatgaaatca gagaagctat acacaagtcc caggacgccg aaacaaaacc cacgttttac 360

gtctgcccac cgccaacagg ctccacaatc gtacgattag aaccaactcg gacatgtccg 420

gattatcacc ttggtaaaaa ctttacagag ggtattgctg ttgtttataa agaaaacatt 480

gcagcgtaca agtttaaggc gacggtatat tacaaagatg ttatcgttag cacggcgtgg 540

gccggaagtt cttatacgca aattactaat agatatgcgg atagggtacc aattcccgtt 600

tcagagatca cggacaccat tgataagttt ggcaagtgtt cttctaaagc aacgtacgta 660

cgaaataacc acaaagttga agcctttaat gaggataaaa atccacagga tatgcctcta 720

atcgcatcaa aatataattc tgtgggatcc aaagcatggc atactaccaa tgacacgtac 780

atggttgccg gaacccccgg aacatatagg acgggcgcgt cggtgaattg catcattgag 840

gaagttgaag ccagatcaat attcccttat gatagttttg gactttccac gggagatata 900

atatacatgt ccccgttttt tggcctacgg gatggtgcat acagagaaca ttccaattat 960

gcaatggatc gttttcacca gtttgagggt tatagacaaa gggatcttga cactagagca 1020

ttactggaac ctgcagcgcg gaacttttta gtcacgcctc atttaacggt tggttggaac 1080

tggaagccaa aacgaacgga agtttgttcg cttgtcaagt ggcgtgaggt tgaagacgta 1140

gttcgcgatg agtatgcaca caattttcgc tttacaatga aaacactttc taccacgttt 1200

ataagtgaaa caaacgagtt taatcttaac caaatccatc tcagtcaatg tgtaaaggag 1260

gaagcccggg ctattattaa ccggatctat acaaccagat acaactcatc tcatgttaga 1320

accggggata tccagaccta ccttgccaga ggggggtttg ttgtggtgtt tcaacccctg 1380

ctgagcaatt ccctcgcccg tctctatctc caagaattgg tccgtgaaaa cactaatcat 1440

tcaccacaaa aacacccgac tcgaaatacc agatcccgac gaagcgtgcc agttgagttg 1500

cgtgccaata gaacaataac aaccacctca tcggtggaat ttgctatgct ccagtttaca 1560

tatgaccaca ttcaagagca tgttaatgaa atgttggcac gtatctcctc gtcgtggtgc 1620

cagctacaaa atcgcgaacg cgccctttgg agcggactat ttccaattaa cccaagtgct 1680

ttagcgagca ccattttgga tcaacgtgtt aaagctcgta ttctcggcga cgttatctcc 1740

gtttctaatt gtccagaact gggatcagat acacgcatta tacttcaaaa ctctatgagg 1800

gtatctggta gtactacgcg ttgttatagc cgtcctttaa tttcaatagt tagtttaaat 1860

gggtccggga cggtggaggg ccagcttgga acagataacg agttaattat gtccagagat 1920

ctgttagaac catgcgtggc taatcacaag cgatattttc tatttgggca tcactacgta 1980

tattatgagg attatcgtta cgtccgtgaa atcgcagtcc atgatgtggg aatgattagc 2040

acttacgtag atttaaactt aacacttctt aaagatagag agtttatgcc gctgcaagta 2100

tatacaagag acgagctgcg ggatacagga ttactagact acagtgaaat tcaacgccga 2160

aatcaaatgc attcgctgcg tttttatgac atagacaagg ttgtgcaata tgatagcgga 2220

acggccatta tgcagggcat ggctcagttt ttccagggac ttgggaccgc gggccaggcc 2280

gttggacatg tggttcttgg ggccacggga gcgctgcttt ccaccgtaca cggatttacc 2340

acgtttttat ctaacccatt tggggcattg gccgtgggat tattggtttt ggcgggactg 2400

gtagcggcct tttttgcgta ccggtacgtg cttaaactta aaacaagccc gatgaaggca 2460

ttatatccac tcacaaccaa ggggttaaaa cagttaccgg aaggaatgga tccctttgcc 2520

gagaaaccca acgctactga taccccaata gaagaaattg gcgactcaca aaacactgaa 2580

ccgtcggtaa atagcgggtt tgatcccgat aaatttcgag aagcccagga aatgattaaa 2640

tatatgacgt tagtatctgc ggctgagcgc caagaatcta aagcccgcaa aaaaaataag 2700

actagcgccc ttttaacttc acgtcttacc ggccttgctt tacgaaatcg ccgaggatac 2760

tcccgtgttc gcaccgagaa tgtaacgggg gtgtaa 2796

<210> 93

<211> 2574

<212> DNA

<213> artificial sequence

<220>

<223> Domain I SNP A604G gB4-1 EBV 1 type strain B95-8/Raji

<400> 93

atgactcggc gtagggtgct aagcgtggtc gtgctgctag ccgccctggc gtgccgtctc 60

ggtgcgcaga ccccagagca gcccgcaccc cccgccacca cggtgcagcc taccgccacg 120

cgtcagcaaa ccagctttcc tttccgagtc tgcgagctct ccagccacgg cgacctgttc 180

cgcttctcct cggacatcca gtgtccctcg tttggcacgc gggagaatca cacggagggc 240

ctgttgatgg tgtttaaaga caacattatt ccctactcgt ttaaggtccg ctcctacacc 300

aagatagtga ccaacattct catctacaat ggctggtacg cggactccgt gaccaaccgg 360

cacgaggaga agttctccgt tgacagctac gaaactgacc agatggatac catctaccag 420

tgctacaacg cggtcaagat gacaaaagat gggctgacgc gcgtgtatgt agaccgcgac 480

ggagttaaca tcaccgtcaa cctaaagccc accgggggcc tggccaacgg ggtgcgccgc 540

tacgccagcc agacggagct ctatgacgcc cccgggtggt tgatatggac ttacagaaca 600

agagctaccg tcaactgcct gataactgac atgatggcca agtccaacag ccccttcgac 660

ttctttgtga ccaccaccgg gcagactgtg gaaatgtccc ctttctatga cgggaaaaat 720

aaggaaacct tccatgagcg ggcagactcc ttccacgtga gaactaacta caagatagtg 780

gactacgaca accgagggac gaacccgcaa ggcgaacgcc gagccttcct ggacaagggc 840

acttacacgc tatcttggaa gctcgagaac aggacagcct actgcccgct tcaacactgg 900

caaacctttg actcgaccat cgccacagaa acagggaagt caatacattt tgtgactgac 960

gagggcacct ctagcttcgt gaccaacaca accgtgggca tagagctccc ggacgccttc 1020

aagtgcatcg aagagcaggt gaacaagacc atgcatgaga agtacgaggc cgtccaggat 1080

cgttacacga agggccagga agccattaca tattttataa cgagcggagg attgttatta 1140

gcttggctac ctctgacccc gcgctcgttg gccaccgtca agaacctgac ggagcttacc 1200

actccgactt cctcaccccc cagcagtcca tcgcccccag ccccatccgc ggcccgcggg 1260

agcacccccg ccgccgttct gaggcgtcgg aggcgggatg cggggaacgc caccacaccg 1320

gtgcccccca cggcccccgg gaagtccctg ggcaccctca acaatcccgc caccgtccag 1380

atccaatttg cctacgactc cctgcgccgc cagatcaacc gcatgctggg agaccttgcg 1440

cgggcctggt gcctggagca gaagaggcag aacatggtgc tgagagaact aaccaagatt 1500

aatccaacca ccgtcatgtc cagcatctac ggtaaggcgg tggcggccaa gcgcctgggg 1560

gatgtcatct cagtctccca gtgcgtgccc gttaaccagg ccaccgtcac cctgcgcaag 1620

agcatgaggg tccctggctc cgagaccatg tgctactcgc gccccctggt gtccttcagc 1680

tttatcaacg acaccaagac ctacgaggga cagctgggca ccgacaacga gatcttcctc 1740

acaaaaaaga tgacggaggt gtgccaggcg accagccagt actacttcca gtccggcaac 1800

gagatccacg tctacaacga ctaccaccac tttaaaacca tcgagctgga cggcattgcc 1860

accctgcaga ccttcatctc actaaacacc tccctcatcg agaacattga ctttgcctcc 1920

ctggagctgt actcacggga cgaacagcgt gcctccaacg tctttgacct ggagggcatc 1980

ttccgggagt acaacttcca ggcgcaaaac atcgccggcc tgcggaagga tttggacaat 2040

gcagtgtcaa acggaagaaa tcaattcgtg gacggcctgg gggaacttat ggacagtctg 2100

ggtagcgtgg gtcagtccat caccaaccta gtcagcacgg tggggggttt gtttagcagc 2160

ctggtctctg gtttcatctc cttcttcaaa aaccccttcg gcggcatgct cattctggtc 2220

ctggtggcgg gggtggtgat cctggttatt tccctcacga ggcgcacgcg ccagatgtcg 2280

cagcagccgg tgcagatgct ctaccccggg atcgacgagc tcgctcagca acatgcctct 2340

ggtgagggtc caggcattaa tcccattagt aagacagaat tacaagccat catgttagcg 2400

ctgcatgagc aaaaccagga gcaaaagaga gcagctcaga gggcggccgg accctcagtg 2460

gccagcagag cattgcaggc agccagggac cgttttccag gcctacgcag aagacgctat 2520

cacgatccag agaccgccgc cgcactgctt ggggaggcag agactgagtt ttaa 2574

<210> 94

<211> 2574

<212> DNA

<213> artificial sequence

<220>

<223> Domain I SNP A604G gB4-2 EBV 2-type strain AG876

<400> 94

atgactcggc gtagggtgct aagcgtggtc gtgctgctag ccgccctggc gtgccgcctc 60

ggtgcgcaga ccccagagca gcccgcaccc cccgccacca cggtgcagcc taccgccacg 120

cgtcagcaaa ccagctttcc tttccgagtc tgcgagctct ccagccacgg cgacctgttc 180

cgcttctcct cggacatcca gtgtccctcg tttggcacgc gggagaatca cacggagggc 240

ctgttgatgg tgtttaaaga caacattatt ccctactcgt ttaaggtccg ctcctacacc 300

aagatagtga ccaacattct catctacaat ggctggtacg cggactccgt gaccaaccgg 360

cacgaggaga agttctccgt tgacagctac gaaactgacc agatggatac catctaccag 420

tgctacaacg cggtcaagat gacaaaagat gggctgacgc gcgtgtatgt agaccgcgac 480

ggagttaaca tcaccgtcaa cctaaagccc accgggggcc tggccaacgg ggtgcgccgc 540

tacgccagcc agacggagct ctatgacgcc cccgggtggt tgatatggac ttacagaaca 600

agagctaccg tcaactgcct gataactgac atgatggcca agtccaacag ccccttcgac 660

ttctttgtga ccaccaccgg gcagactgtg gaaatgtccc ctttctatga cgggaaaaat 720

aaggaaacct tccatgagcg ggcagactcc ttccacgtga gaactaacta caagatagtg 780

gactacgaca accgagggac gaacccgcaa ggcgaacgcc gagccttcct ggacaagggc 840

acttacaccc tatcttggaa gctcgagaac aggacagcct actgcccgct tcaacactgg 900

caaacctttg actcgaccat cgccacagaa acagggaagt caatacattt tgtgactgac 960

gagggcacct ctagcttcgt gaccaacaca accgtgggca tagagctccc ggacgccttc 1020

aagtgcatcg aagagcaggt gaacaagacc atgcatgaga agtacgaggc cgtccaggat 1080

cgttacacga agggccagga agccattaca tattttataa cgagcggagg attgttatta 1140

gcttggctac ctctgacccc gcgctcgttg gccaccgtca agaacctgac ggagcttacc 1200

actccgactt cctcaccccc cagcagtcca tcgccccccg ccccacccgc ggcccgcggg 1260

agcacctccg ccgccgttct gaggcgccgg aggcgggatg cggggaatgc caccacaccg 1320

gtgccccccg cggcccccgg gaagtccctg ggcaccctca acaatcccgc caccgtccag 1380

atccaatttg cctacgattc cctgcgccgc cagatcaacc gcatgctggg agacctcgcg 1440

cgggcctggt gcctggagca gaagaggcag aacatggtgc tgagagaact aaccaagatt 1500

aatcccacca ccgtcatgtc cagcatctac ggtaaggcgg tggcggccaa gcgcctgggg 1560

gatgtcatct cagtctccca gtgcgtgccc gttaaccagg ccaccgtcac cctgcgcaag 1620

agcatgaggg tccctggctc cgagaccatg tgctactcgc gccccctggt gtccttcagc 1680

tttatcaacg acaccaagac ctacgaggga cagctgggca ccgacaacga gatcttcctc 1740

acaaaaaaga tgacggaggt gtgccaggcg accagccagt actacttcca gtccggcaac 1800

gagatccacg tctacaacga ctaccaccac tttaaaacca tcgagctgga cggcattgcc 1860

accctgcaga ccttcatctc actaaacacc tccctcatcg agaacattga ctttgcctcc 1920

ctggagctgt actcacggga cgaacagcgt gcctccaacg tctttgacct ggagggcatc 1980

ttccgggagt acaacttcca ggcgcaaaac atcgccggcc tgcggaagga tttggacaat 2040

gcagtgtcaa acggaagaaa tcaattcgtg gacggcctgg gggaacttat ggacagtctg 2100

ggtagcgtgg gtcagtccat caccaaccta gtcagcacgg tggggggttt gtttagcagc 2160

ctggtctctg gtttcatctc cttcttcaaa aaccccttcg gcggcatgct cattctggtc 2220

ctggtggcgg gggtggtgat cctggttatt tccctcacga ggcgcacgcg ccagatgtcg 2280

cagcagccgg tgcagatgct ctaccccggg atcgacgagc tcgctcagca acatgcctct 2340

ggtgagggtc caggcattaa tcccattagt aagacagaat tacaagccat catgttagcg 2400

ctgcatgagc aaaaccagga gcaaaagaga gcagctcaga gggcggccgg accctcagtg 2460

gccagcagag cattgcaggc agccagggac cgttttccag gcctacgcag aagacgctat 2520

cacgatccag agaccgccgc cgcactgctt ggggaggcag agactgagtt ttaa 2574

<210> 95

<211> 2724

<212> DNA

<213> artificial sequence

<220>

<223> Domain I SNP A733G gB5 HCMV strain Merlin

<400> 95

atggaatcca ggatctggtg cctggtagtc tgcgttaact tgtgtatcgt ctgtctgggt 60

gctgcggttt cctcatcttc tactcgtgga acttctgcta ctcacagtca ccattcctct 120

catacgacgt ctgctgctca ctctcgatcc ggttcagtct ctcaacgcgt aacttcttcc 180

caaacggtca gccatggtgt taacgagacc atctacaaca ctaccctcaa gtacggagat 240

gtggtggggg tcaataccac caagtacccc tatcgcgtgt gttctatggc ccagggtacg 300

gatcttattc gctttgaacg taatatcgtc tgcacctcga tgaagcccat caatgaagac 360

ctggacgagg gcatcatggt ggtctacaaa cgcaacatcg tcgcgcacac ctttaaggta 420

cgagtctacc agaaggtttt gacgtttcgt cgtagctacg cttacatcca caccacttat 480

ctgctgggca gcaacacgga atacgtggcg cctcctatgt gggagattca tcatatcaac 540

agccacagtc agtgctacag ttcctacagc cgcgttatag caggcacggt tttcgtggct 600

tatcataggg acagctatga aaacaaaacc atgcaattaa tgcccgacga ttattccaac 660

acccacagta cccgttacgt gacggtcaag gatcaatggc acagccgcgg cagcacctgg 720

ctctatcgtg aggcctgtaa tctgaattgt atggtgacca tcactactgc gcgctccaaa 780

tatccttatc attttttcgc cacttccacg ggtgacgtgg ttgacatttc tcctttctac 840

aacggaacca atcgcaatgc cagctacttt ggagaaaacg ccgacaagtt tttcattttt 900

ccgaactaca ctatcgtctc cgactttgga agaccgaatt ctgcgttaga gacccacagg 960

ttggtggctt ttcttgaacg tgcggactcg gtgatctcct gggatataca ggacgaaaag 1020

aatgtcactt gtcaactcac tttctgggaa gcctcggaac gcaccattcg ttccgaagcc 1080

gaggactcgt atcacttttc ttctgccaaa atgaccgcca ctttcttatc taagaagcaa 1140

gaggtgaaca tgtccgactc tgcgctggac tgcgtacgtg atgaggctat aaataagtta 1200

cagcagattt tcaatacttc atacaatcaa acatatgaaa aatatggaaa cgtgtccgtc 1260

tttgaaacca ctggtggttt ggtagtgttc tggcaaggta tcaagcaaaa atctctggtg 1320

gaactcgaac gtttggccaa ccgctccagt ctgaatctta ctcataatag aaccaaaaga 1380

agtacagatg gcaacaatgc aactcattta tccaacatgg aatcggtgca caatctggtc 1440

tacgcccagc tgcagttcac ctatgacacg ttgcgcggtt acatcaaccg ggcgctggcg 1500

caaatcgcag aagcctggtg tgtggatcaa cggcgcaccc tagaggtctt caaggaactc 1560

agcaagatca acccgtcagc cattctctcg gccatttaca acaaaccgat tgccgcgcgt 1620

ttcatgggtg atgtcttggg cctggccagc tgcgtgacca tcaaccaaac cagcgtcaag 1680

gtgctgcgtg atatgaacgt gaaggagtcg ccaggacgct gctactcacg acccgtggtc 1740

atctttaatt tcgccaacag ctcgtacgtg cagtacggtc aactgggcga ggacaacgaa 1800

atcctgttgg gcaaccaccg cactgaggaa tgtcagcttc ccagcctcaa gatcttcatc 1860

gccgggaact cggcctacga gtacgtggac tacctcttca aacgcatgat tgacctcagc 1920

agtatctcca ccgtcgacag catgatcgcc ctggatatcg acccgctgga aaataccgac 1980

ttcagggtac tggaacttta ctcgcagaaa gagctgcgtt ccagcaacgt ttttgacctc 2040

gaagagatca tgcgcgaatt caactcgtac aagcagcggg taaagtacgt ggaggacaag 2100

gtagtcgacc cgctaccgcc ctacctcaag ggtctggacg acctcatgag cggcctgggc 2160

gccgcgggaa aggccgttgg cgtagccatt ggggccgtgg gtggcgcggt ggcctccgtg 2220

gtcgaaggcg ttgccacctt cctcaaaaac cccttcggag cgttcaccat catcctcgtg 2280

gccatagctg tagtcattat cacttatttg atctatactc gacagcggcg tttgtgcacg 2340

cagccgctgc agaacctctt tccctatctg gtgtccgccg acgggaccac cgtgacgtcg 2400

ggcagcacca aagacacgtc gttacaggct ccgccttcct acgaggaaag tgtttataat 2460

tctggtcgca aaggaccggg accaccgtcg tctgatgcat ccacggcggc tccgccttac 2520

accaacgagc aggcttacca gatgcttctg gccctggccc gtctggacgc agagcagcga 2580

gcgcagcaga acggtacaga ttctttggac ggacggactg gcacgcagga caagggacag 2640

aagcccaacc tactagaccg actgcgacat cgcaaaaacg gctaccgaca cttgaaagac 2700

tctgacgaag aagagaacgt ctga 2724

<210> 96

<211> 2493

<212> DNA

<213> artificial sequence

<220>

<223> Domain I SNP A577G gB6A HHV6A Strain U1102

<400> 96

atgagcaaga tggcagtatt attcctggct gtctttttga tgaatagtgt tttaatgata 60

tattgtgatc cggatcatta tatcagagcg ggctataatc acaaatatcc ttttcggatt 120

tgttcgattg ccaaaggcac ggatttaatg cggttcgaca gagatatttc gtgctcgccg 180

tataagtcta atgcaaagat gtcggagggt tttttcatca tttacaaaac aaatatcgag 240

acctacactt ttccagtgag aacgtataaa aaagagttga cgttccaaag tagttaccgt 300

gatgtgggtg tggtttattt tctggatcgg acggtgatgg gtttggccat gccggtgtac 360

gaagcaaatt tagttaattc tcatgcgcag tgttattccg ccgtagcgat gaaacgaccc 420

gatggtacgg tgtttagtgc ctttcatgag gataataata aaaacaatac tctaaattta 480

tttcctctga atttcaaatc tataactaat aaaagattta tcactacgaa agaaccctac 540

tttgcaaggg gtcctttgtg gctatattct acatcagcgt ctctcaattg tattgtgacg 600

gaggctacgg ctaaggcgaa atacccgttt agttactttg ctttgacgac tggcgaaatc 660

gtggaagggt ctccgttctt caacggttca aacggtaaac attttgcaga gccgttagaa 720

aaattgacaa tcttggaaaa ctatactatg atagaagatc taatgaatgg tatgaatggg 780

gccactacgt tagtgaggaa aatcgctttt ctcgagaaag cggatacttt gttttcttgg 840

gaaatcaagg aagagaatga atcggtgtgt atgctaaagc actggaccac ggtgactcac 900

gggcttcgag cggagacgaa tgagacctat cactttatct ctaaggagtt gacagccgct 960

ttcgtcgccc ccaaggagtc cttaaatctt accgatccga aacaaacgtg tattaagaat 1020

gaatttgaaa aaataattaa tgaagtctat atgtcagatt ataatgatac atatagcatg 1080

aatggtagtt atcaaatttt taagactacg ggagatttga ttttgatttg gcaacctctt 1140

gtgcaaaaat ctcttatgtt tcttgagcag ggttcggaaa aaatacgtag gaggcgagat 1200

gtgggggatg ttaagtctag acatgatatt ctttatgtgc aattacagta tctttatgat 1260

actttgaaag attatatcaa tgatgcattg gggaatttgg cagaatcttg gtgtctcgat 1320

caaaagcgaa cgataacgat gttgcacgaa cttagtaaga ttagtccgtc gagtatcgtg 1380

tctgaggttt acggtcgtcc gatatctgca cagttgcatg gtgacgtgtt agctatctcg 1440

aaatgcatag aggttaatca gtcatccgtt cagcttcata agagtatgcg ggtcgtcgat 1500

gcaaagggag taaggagtga aacgatgtgt tataatcggc ccttggtgac gtttagtttt 1560

gtgaactcga cgcctgaggt tgtccctggc cagctagggt tagataatga aattctgttg 1620

ggtgatcata ggacagagga atgtgaaata cctagtacaa agatcttttt atctggaaat 1680

catgcgcacg tgtataccga ttatacgcat acgaattcga cgcccataga agacattgag 1740

gtattggatg cttttattag actaaaaatc gatcctcttg aaaatgccga ttttaaagta 1800

ctcgatttat attcgccgga cgaattgagt agagcaaacg ttttcgatct agagaatatt 1860

cttcgtgaat ataactcata taagagcgca ctatatacta tagaagctaa aattgctacg 1920

aatacacctt cgtatgttaa tgggattaat tcttttttac aagggcttgg ggctataggc 1980

actggattgg gctcggttat aagtgttacg gcaggagcgc ttggggatat tgtgggtgga 2040

gtggtgtctt ttctaaaaaa tccattcggg ggtggtctca tgttgatttt agcgatagta 2100

gttgttgtga taataattgt ggttttcgtt agacaaagac atgtgcttag taagcctatt 2160

gacatgatgt ttccttatgc caccaatccg gtgactactg tgtccagtgt tacggggacc 2220

actgtcgtca agacacctag tgttaaggat gttgacgggg gcacatctgt tgcggtttcg 2280

gaaaaggagg agggtatggc tgacgtcagt gggcaagtaa gtgacgatga atattcacaa 2340

gaagatgctt taaaaatgct caaggccata aagtccttag acgagtccta cagaagaaaa 2400

ccttcgtctt ctgagtctca tgcctcaaaa cctagtttga tagacaggat caggtataga 2460

ggttataaga gtgtaaatgt agaagaagcg tga 2493

<210> 97

<211> 2493

<212> DNA

<213> artificial sequence

<220>

<223> Domain I SNP A577G gB6B HHV6B Strain Z29

<400> 97

atgagcaaga tgagagtatt attcctggct gtctttttga tgaatagtgt tttaatgata 60

tattgcgatt cggatgatta tatcagagcg ggctataatc acaaatatcc ttttcggatt 120

tgttcgattg ccaaaggcac tgatttgatg cggttcgaca gagatatttc gtgttcgcca 180

tataagtcta atgcaaagat gtcggagggt tttttcatca tttacaaaac aaatatcgag 240

acctacactt ttccagtgag aacatataaa aacgagctga cgttcccaac cagttaccgt 300

gatgtgggtg tggtttattt tctggatcgg acggtgatgg gtttggccat gccggtgtac 360

gaagcaaatt tagttaattc tcgtgcgcag tgttattcag ccgtagcgat aaaacgaccc 420

gatggtacgg tgtttagtgc ctatcatgag gataataata aaaacgaaac tctagaatta 480

tttcctctga atttcaagtc tgttactaat aaaagattta tcactacgaa agaaccctac 540

tttgcaaggg gtcctttgtg gctctattct acatcggcgt ctctcaattg tattgtgacg 600

gaggctacgg ctaaggcgaa atatccgttt agttactttg ctttgacgac tggtgaaatc 660

gtggaagggt ctccgttctt cgacggttca aacggtaaac attttgcaga gccgttagaa 720

aaattgacaa tcttggaaaa ctatactatg atagaagatc taatgaatgg tatgaatggg 780

gctactacgt tagtaaggaa gatcgctttt ctggagaaag gggatacttt gttttcttgg 840

gaaatcaagg aagagaatga atcggtgtgt atgctaaagc actggactac ggtgactcac 900

gggcttcgag cggagacgga tgagacttat cactttattt ctaaggagtt gacagccgct 960

ttcgtcgcct ccaaggagtc tttaaatctt accgatccca aacaaacgtg tattaagaat 1020

gaatttgaga agataattac agatgtctat atgtcagatt ataatgatgc atacagcatg 1080

aacggtagtt atcaaatttt taagactacg ggagatctga ttttgatttg gcagcctctt 1140

gtgcaaaaat ctcttatggt tcttgagcag ggttcagtaa acttacgtag gaggcgagat 1200

ttggtggatg tcaagtctag acatgatatt ctttatgtgc aattacagta cctctatgat 1260

actttgaaag attatatcaa cgatgccttg gggaatttgg cagaatcttg gtgcctcgat 1320

caaaaacgaa cgataacgat gttgcacgaa cttagtaaga tcagtccatc gagtatcgtg 1380

tctgaggttt acggtcgtcc gatatctgca cagttgcatg gtgatgtgtt agctatctcg 1440

aaatgcatag aagttaatca atcatccgtt cagctttata agagtatgcg ggtcgtcgat 1500

gcgaagggag taaggagtga aacgatgtgt tataatcggc ccttggtgac gtttagcttt 1560

gtgaactcca cgcctgaggt tgtccttggt cagctagggt tagataatga gattctgttg 1620

ggtgatcata ggacagagga atgtgagata cctagtacaa agatatttct atctggaaat 1680

catgcacacg tgtataccga ttatacgcat acgaattcga cgcccataga agacattgag 1740

gtattggatg cttttattag actaaagatc gaccctctcg aaaatgctga ttttaaacta 1800

cttgatttat attcgccgga cgaattgagt agagcaaacg ttttcgattt agagaatatt 1860

cttcgtgaat ataactcata taagagcgca ctatatacta tagaagctaa aattgctact 1920

aatacgccgt cgtatgtcaa tgggattaat tcttttttac aagggcttgg ggctataggc 1980

actggattgg gctcggttat aagtgttacg gcaggagcac ttggggatat tgtgggtgga 2040

gtggtgtctt ttttaaaaaa tccattcggg ggtggtctca tgttgatttt agcgatagta 2100

gttgtcgtta taataattgt ggttttcgtt agacaaaaac atgtgcttag taagcctatt 2160

gacatgatgt ttccttatgc caccaatccg gtgactactg tgtccagtgt tacggggacc 2220

actgtcgtca agacgcctag tgttaaagat gctgacgggg gcacatctgt tgcggtttcg 2280

gaaaaagagg agggtatggc tgacgtcagt ggacaaataa gtggtgatga atattcacaa 2340

gaagatgctt taaaaatgct caaggccata aagtctttag acgagtccta cagaagaaaa 2400

ccttcgtctt ctgagtctca tgcctcaaaa cctagtttga tagacaggat caggtataga 2460

ggttataaga gtgtaaatgt agaagaagcg tga 2493

<210> 98

<211> 2469

<212> DNA

<213> artificial sequence

<220>

<223> Domain I SNP A568G gB7 HHV7 Strain RK

<400> 98

atgaaaattc tattcctgag tgtttttata acttttagct tacagctatc tctacaaaca 60

gaagctgact ttgtcatgac tggacacaat cagcatttac catttcgaat ttgttcaatt 120

gccaccggga cagatttagt gcgttttgac agggaggttt cttgcgcgtc ttacggctct 180

aacattaaaa ctaccgaagg tattttgata atttacaaaa caaagattga agcacacacg 240

ttttctgtca gaacttttaa aaaagaactt acatttcaaa caacatatcg cgatgttggc 300

actgtgtatt tcttagatcg aactgttaca actttgccaa tgccaattga agaagtgcac 360

atggtaaaca ccgaggcgcg ttgtttgtcc tctatctctg taaaacgttc ggaggaagag 420

gagtatgttg catatcataa agatgaatat gtgaataaaa cgttggattt gattccgtta 480

aattttaaat ctgatactgt cagaagatat ataactacta aagaaccatt tttaagaaat 540

ggtcccctct ggttctattc aacatctgca tcgataaatt gcatagttac agactgcatt 600

gcaaagacta aatatccttt tgattttttt gctttatcaa caggggaaac cgtggaaggg 660

tcaccgtttt ataatggtat taattctaaa acatttaatg aaccaacgga aaaaattttg 720

tttagaaata attatactat gctgaaaacg tttgatgatg gatcaaaagg aaattttgtg 780

acgttaacta aaatggcttt tctggaaaag ggaaatacta ttttttcatg ggaagtgcag 840

aatgaagagt cttccatttg tttgttaaag cattggatga caatcccaca cgctttacgg 900

gcagaaaatg ctaacagttt tcactttatt gcgcaggaac taactgcttc ttttgtcaca 960

ggaaaaagta attatacgct ttctgattca aaatataatt gtattaacag caattatact 1020

tcaattttgg atgagattta ccaaacgcaa tacaacaatt cgcatgacaa aaatggtagt 1080

tatgaaattt ttaaaactga gggagattta attctgattt ggcaaccgtt aatacaacgg 1140

aaattaacgg ttttggaaaa tttttctaat gcttctagaa aaaggaggaa gagggaatta 1200

gagactaaca aagacatcgt atatgttcaa ctacaatacc tatacgacac tctgaaagat 1260

tacattaaca cagcactagg taagcttgct gaagcctggt gtttagatca aaaacgcact 1320

atcacagtgt tgcacgagct tagtaaaata agtccttctg gaatcatttc agcagtgtac 1380

ggtaaaccca tgtccgctaa attaattggt gatgtattag cagtctcaaa gtgcattgaa 1440

gtcaaccaga cttctgttca gctacataaa agtatgagat tgacaaaaga ttcaagttac 1500

gatgctctaa gatgttattc tcggccattg ttaacatatt catttgcaaa ttcttcgaag 1560

gaaacttatt taggacaact tggtttagac aatgagatat tactgggaaa tcacagaaca 1620

gaagaatgtg aacaatctaa cacgaaaatt tttttgtctg gtaaattcgc tcatattttt 1680

aaagactata cgtacgttaa ttctagtttg ataacagaaa tagaagcttt agatgcgttt 1740

gttgacttaa acatagatcc tttagaaaat gcagatttta cattattgga attgtataca 1800

aaagatgaac tgagcaaagc gaacgttttt gatttggaaa ccattcttag agaatacaat 1860

tcttacaaaa gtgcgctaca ccatatagaa acaaaaattg caactgttac tccaacatat 1920

ataggaggga ttgacacatt tttcaaaggt cttggcgctc ttggtcttgg tttgggggct 1980

gtgctgggtg taacggctgg tgctttggga gatgtggtga atggagtttt ctcttttctt 2040

aaaaatccat ttggtggagc actaactatc ttactaactt tgggagtgat tggcttagtt 2100

attttcttat ttttaagaca taaacgatta gcacaaacac cgattgatat tttatttcct 2160

tatacatcaa aatcaacaaa ttcggtactt caagcaacgc aatcagttca agcgcaagtg 2220

aaagaacctt tagattcatc tccgccttat ttaaaaacta acaaagacac agaaccgcaa 2280

ggtgatgaca taacacacac taatgaatat tcacaagtgg aagctttaaa aatgttgaaa 2340

gctattaaat tattagatga gtcatataaa aaagcggaaa tcgctgaggc aaaaaaatca 2400

cagagaccaa gcctacttga aaggattcaa tacaggggct atcagaaact ttcaacagaa 2460

gaactgtga 2469

<210> 99

<211> 2538

<212> DNA

<213> artificial sequence

<220>

<223> Domain I SNP A652G gB8 HHV8 strain GK18

<400> 99

atgactccca ggtctagatt ggccaccctg gggactgtca tcctgttggt ctgcttttgc 60

gcaggcgcgg cgcactcgag gggtgacacc tttcagacgt ccagttcccc cacaccccca 120

ggatcttcct ctaaggcccc caccaaacct ggtgaggaag catctggtcc taagagtgtg 180

gacttttacc agttcagagt gtgtagtgca tcgatcaccg gggagctttt tcggttcaac 240

ctggagcaga cgtgcccaga caccaaagac aagtaccacc aagaaggaat tttactggtg 300

tacaaaaaaa acatagtgcc tcatatcttt aaggtgcggc gctataggaa aattgccacc 360

tctgtcacgg tctacagggg cttgacagag tccgccatca ccaacaagta tgaactcccg 420

agacccgtgc cactctatga gataagccac atggacagca cctatcagtg ctttagttcc 480

atgaaggtaa atgtcaacgg ggtagaaaac acatttactg acagagacga tgttaacacc 540

acagtattcc tccaaccagt agaggggctt acggataaca ttcaaaggta ctttagccag 600

ccggtcatct acgcggaacc cggctggttt cccggcatat acagagttag ggccaccgtc 660

aattgcgaga tagtggacat gatagccagg tctgctgaac catacaatta ctttgtcacg 720

tcactgggtg acacggtgga agtctcccct ttttgctata acgaatcctc atgcagcaca 780

acccccagca acaaaaatgg ccttagcgtc caagtagttc tcaaccacac tgtggtcacg 840

tactctgaca gaggaaccag tcccactccc caaaacagga tctttgtgga aacgggagcg 900

tacacgcttt cgtgggcctc cgagagcaag accacggccg tgtgtccgct ggcactgtgg 960

aaaaccttcc cgcgctccat ccagactacc cacgaggaca gcttccactt tgtggccaac 1020

gagatcacgg ccaccttcac ggctcctcta acgccagtgg ccaactttac cgacacgtac 1080

tcttgtctga cctcggatat caacaccacg ctaaacgcca gcaaggccaa actggcgagc 1140

actcacgtcc ctaacgggac ggtccagtac ttccacacaa caggcggact ctatttggtc 1200

tggcagccca tgtccgcgat taacctgact cacgctcagg gcgacagcgg gaaccccacg 1260

tcatcgccgc ccccctccgc atcccccatg accacctctg ccagccgcag aaagagacgg 1320

tcagccagta ccgctgctgc cggcggcggg gggtccacgg acaacctgtc ttacacgcag 1380

ctgcagtttg cctacgacaa actgcgggat ggcattaatc aggtgttaga agaactctcc 1440

agggcatggt gtcgcgagca ggtcagggac aacctaatgt ggtacgagct cagtaaaatc 1500

aaccccacca gcgttatgac agccatctac ggtcgacctg tatccgccaa gttcgtagga 1560

gacgccattt ccgtgaccga gtgcattaac gtggaccaga gctccgtaaa catccacaag 1620

agcctcagaa ccaatagtaa ggacgtgtgt tacgcgcgcc ccctggtgac gtttaagttt 1680

ttgaacagtt ccaacctatt caccggccag ctgggcgcgc gcaatgagat aatactgacc 1740

aacaaccagg tggaaacctg caaagacacc tgcgaacact acttcatcac ccgcaacgag 1800

actctggtgt ataaggacta cgcgtacctg cgtactataa acaccactga catatccacc 1860

ctgaacactt ttatcgccct gaatctatcc tttattcaaa acatagactt caaggccatc 1920

gagctgtaca gcagtgcaga gaaacgactc gcgagtagcg tgtttgacct ggagacgatg 1980

ttcagggagt acaactacta cacacatcgt ctcgcgggtt tgcgcgagga tctggacaac 2040

accatagata tgaacaagga gcgcttcgta agggacttgt cggagatagt ggcggacctg 2100

ggtggcatcg gaaaaacggt ggtgaacgtg gccagcagcg tggtcactct atgtggctca 2160

ttggttaccg gattcataaa ttttattaaa caccccctag gtggcatgct gatgatcatt 2220

atcgttatag caatcatcct gatcattttt atgctcagtc gccgcaccaa taccatagcc 2280

caggcgccgg tgaagatgat ctaccccgac gtagatcgca gggcacctcc tagcggcgga 2340

gccccaacac gggaggaaat caaaaacatc ctgctgggaa tgcaccagct acaacaagag 2400

gagaggcaga aggcggatga tctgaaaaaa agtacaccct cggtgtttca gcgtaccgca 2460

aacggccttc gtcagcgtct gagaggatat aaacctctga ctcaatcgct agacatcagt 2520

ccggaaacgg gggagtga 2538

<210> 100

<211> 675

<212> DNA

<213> human herpesvirus 1 strain 17

<220>

<223> NC_001806.2:9338-10012 human herpesvirus 1 strain 17,

glycoprotein gL-UL1

<400> 100

atggggattt tgggttgggt cgggcttatt gccgttgggg ttttgtgtgt gcgggggggc 60

ttgccttcaa ccgaatatgt tattcggagt cgggtggctc gagaggtggg ggatatatta 120

aaggtgcctt gtgtgccgct cccgtctgac gatcttgatt ggcgttacga gaccccctcg 180

gctataaact atgctttgat agacggtata tttttgcgtt atcactgtcc cggattggac 240

acggtcttgt gggataggca tgcccagaag gcatattggg ttaacccctt tttatttgtg 300

gcgggttttt tggaggactt gagttacccc gcgtttcctg ccaacaccca ggaaacagaa 360

acgcgcttgg ccctttataa agagatacgc caggcgctgg acagtcgcaa gcaggccgcc 420

agccacacac ctgtgaaggc tgggtgtgtg aactttgact attcgcgcac ccgccgctgt 480

gtagggcgac aggatttggg acctaccaac ggaacgtctg gacggacccc ggttctgccg 540

ccggacgatg aagcgggcct gcagccgaag cccctcacca cgccgccgcc catcatcgcc 600

acgtcggacc ccaccccgcg acgggacgcc gccacaaaaa gcagacgccg acgaccccac 660

tcccggcgcc tctaa 675

<210> 101

<211> 2715

<212> DNA

<213> human herpesvirus 2 strain HG52

<220>

<223> NC_001798.2:c56152-53438 human herpesvirus 2 Strain

HG52, glycoprotein B-UL27

<400> 101

atgcgcgggg ggggcttgat ttgcgcgctg gtcgtggggg cgctggtggc cgcggtggcg 60

tcggcggccc cggcggcccc ggcggccccc cgcgcctcgg gcggcgtggc cgcgaccgtc 120

gcggcgaacg ggggtcccgc ctcccggccg ccccccgtcc cgagccccgc gaccaccaag 180

gcccggaagc ggaaaaccaa aaagccgccc aagcggcccg aggcgacccc gccccccgac 240

gccaacgcga ccgtcgccgc cggccacgcc acgctgcgcg cgcacctgcg ggaaatcaag 300

gtcgagaacg ccgatgccca gttttacgtg tgcccgcccc cgacgggcgc cacggtggtg 360

cagtttgagc agccgcgccg ctgcccgacg cgcccggagg ggcagaacta cacggagggc 420

atcgcggtgg tcttcaagga gaacatcgcc ccgtacaaat tcaaggccac catgtactac 480

aaagacgtga ccgtgtcgca ggtgtggttc ggccaccgct actcccagtt tatggggata 540

ttcgaggacc gcgcccccgt tcccttcgag gaggtgatcg acaagattaa cgccaagggg 600

gtctgccgct ccacggccaa gtacgtgcgg aacaacatgg agaccaccgc gtttcaccgg 660

gacgaccacg agaccgacat ggagctcaag ccggcgaagg tcgccacgcg cacgagccgg 720

gggtggcaca ccaccgacct caagtacaac ccctcgcggg tggaggcgtt ccatcggtac 780

ggcacgacgg tcaactgcat cgtcgaggag gtggacgcgc ggtcggtgta cccgtacgat 840

gagtttgtgc tggcgacggg cgactttgtg tacatgtccc cgttttacgg ctaccgggag 900

gggtcgcaca ccgagcacac cagctacgcc gccgaccgct tcaagcaggt cgacggcttc 960

tacgcgcgcg acctcaccac gaaggcccgg gccacgtcgc cgacgacccg caacttgctg 1020

acgaccccca agtttaccgt ggcctgggac tgggtgccga agcgaccggc ggtctgcacc 1080

atgaccaagt ggcaggaggt ggacgagatg ctccgcgccg agtacggcgg ctccttccgc 1140

ttctcctccg acgccatctc gaccaccttc accaccaacc tgaccgagta ctcgctctcg 1200

cgcgtcgacc tgggcgactg catcggccgg gatgcccgcg aggccatcga ccgcatgttt 1260

gcgcgcaagt acaacgccac gcacatcaag gtgggccagc cgcagtacta cctggccacg 1320

gggggcttcc tcatcgcgta ccagcccctc ctcagcaaca cgctcgccga gctgtacgtg 1380

cgggagtaca tgcgggagca ggaccgcaag ccccggaatg ccacgcccgc gccactgcgg 1440

gaggcgccca gcgccaacgc gtccgtggag cgcatcaaga ccacctcctc gatcgagttc 1500

gcccggctgc agtttacgta taaccacata cagcgccacg tgaacgacat gctggggcgc 1560

atcgccgtcg cgtggtgcga gctgcagaac cacgagctga ctctctggaa cgaggcccgc 1620

aagctcaacc ccaacgccat cgcctccgcc accgtcggcc ggcgggtgag cgcgcgcatg 1680

ctcggagacg tcatggccgt ctccacgtgc gtgcccgtcg ccccggacaa cgtgatcgtg 1740

cagaactcga tgcgcgtcag ctcgcggccg gggacgtgct acagccgccc cctggtcagc 1800

tttcggtacg aagaccaggg cccgctgatc gaggggcagc tgggcgagaa caacgagctg 1860

cgcctcaccc gcgacgcgct cgagccgtgc accgtgggcc accggcgcta cttcatcttc 1920

ggcgggggct acgtgtactt cgaggagtac gcgtactctc accagctgag tcgcgccgac 1980

gtcaccaccg tcagcacctt catcgacctg aacatcacca tgctggagga ccacgagttt 2040

gtgcccctgg aggtctacac gcgccacgag atcaaggaca gcggcctgct ggactacacg 2100

gaggtccagc gccgcaacca gctgcacgac ctgcgctttg ccgacatcga cacggtcatc 2160

cgcgccgacg ccaacgccgc catgttcgcg gggctgtgcg cgttcttcga ggggatgggg 2220

gacttggggc gcgcggtcgg caaggtagtc atgggagtag tggggggcgt ggtgtcggcc 2280

gtctcgggcg tgtcctcctt tatgtccaac cccttcgggg cgcttgccgt ggggctgctg 2340

gtcctggccg gcctggtcgc ggccttcttc gccttccgct acgtcctgca actgcaacgc 2400

aatcccatga aggccctgta tccgctcacc accaaggaac tcaagacttc cgaccccggg 2460

ggcgtgggcg gggaggggga ggaaggcgcg gaggggggcg ggtttgacga ggccaagttg 2520

gccgaggccc gagaaatgat ccgatatatg gctttggtgt cggccatgga gcgcacggaa 2580

cacaaggcca gaaagaaggg cacgagcgcc ctgctcagct ccaaggtcac caacatggtt 2640

ctgcgcaagc gcaacaaagc caggtactct ccgctccaca acgaggacga ggccggagac 2700

gaagacgagc tctaa 2715

<210> 102

<211> 2517

<212> DNA

<213> human herpesvirus 2 strain HG52

<220>

<223> NC_001798.2:c46570-44054 human herpesvirus 2 strain

HG52, glycoprotein H-UL22

<400> 102

atgggccccg gtctgtgggt ggtgatgggg gtcctggtgg gcgttgccgg gggccatgac 60

acgtactgga cggagcaaat cgacccgtgg tttttgcacg gtctggggtt ggcccgcacg 120

tactggcgcg acacaaacac cgggcgtctg tggttgccca acacccccga cgccagcgac 180

ccccagcgcg gacgcttggc gcccccgggc gaactcaacc tgactacggc atccgtgccc 240

atgcttcggt ggtacgccga gcgcttttgt ttcgtgttgg tcaccacggc cgagtttcct 300

cgggaccccg ggcagctgct ttacatccca aagacctatc tgctcggccg gcctcggaac 360

gcgagcctgc ccgagctccc cgaggcgggg cccacgtccc gtccccccgc cgaggtgacc 420

cagctcaagg gactgtcgca caaccccggc gcctccgcgc tgttgcggtc ccgggcctgg 480

gtaacattcg cggccgcgcc ggaccgcgag gggcttacgt tcccgcgggg agacgacggg 540

gcgaccgaga ggcacccgga cggccgacgc aacgcgccgc ccccggggcc gcccgcgggg 600

acaccgaggc atccgacgac gaacctgagc atcgcgcatc tgcacaacgc atccgtgacc 660

tggctggccg ccaggggcct gctacggact ccgggtcggt acgtgtacct ctccccgtcg 720

gcctcgacgt ggcccgtggg cgtctggacg acgggcgggc tggcgttcgg gtgcgacgcc 780

gcgctcgtgc gcgcgcgata cgggaagggc ttcatggggc tcgtgatatc gatgcgggac 840

agccctccgg ccgagatcat agtggtgcct gcggacaaga ccctcgctcg ggtcggaaat 900

ccgaccgacg aaaacgcccc cgcggtgctc cccgggcctc cggccggccc caggtatcgc 960

gtctttgtcc tgggggcccc gacgcccgcc gacaacggct cggcgctgga cgccctccgg 1020

cgggtggccg gctaccccga ggagagcacg aactacgccc agtatatgtc gcgggcctat 1080

gcggagtttt tgggggagga cccgggctcc ggcacggacg cgcgtccgtc cctgttctgg 1140

cgcctcgcgg ggctgctcgc ctcgtcgggg tttgcgttcg tcaacgcggc ccacgcccac 1200

gacgcgattc gcctctccga cctgctgggc tttttggccc actcgcgcgt gctggccggc 1260

ctggccgccc ggggagcagc gggctgcgcg gccgactcgg tgttcctgaa cgtgtccgtg 1320

ttggacccgg cggcccgcct gcggctggag gcgcgcctcg ggcatctggt ggccgcgatc 1380

ctcgagcgag agcagagcct ggcggcgcac gcgctgggct atcagctggc gttcgtgttg 1440

gacagccccg cggcctatgg cgcggtggcc ccgagcgcgg cccgcctgat cgacgccctg 1500

tacgccgagt ttctcggcgg ccgcgcgcta accgccccga tggtccgccg agcgctgttt 1560

tacgccacgg ccgtcctccg ggcgccgttc ctggcgggcg cgccctcggc cgagcagcgg 1620

gaacgcgccc gccggggcct cctcataacc acggccctgt gtacgtccga cgtcgccgcg 1680

gcgacccacg ccgatctccg ggccgcgcta gccaggaccg accaccagaa aaacctcttc 1740

tggctcccgg accacttttc cccatgcgca gcttccctgc gcttcgatct cgccgagggc 1800

gggttcatcc tggacgcgct ggccatggcc acccgatccg acatcccggc ggacgtcatg 1860

gcacaacaga cccgcggcgt ggcctccgtt ctcacgcgct gggcgcacta caacgccctg 1920

atccgcgcct tcgtcccgga ggccacccac cagtgtagcg gcccgtcgca caacgcggag 1980

ccccggatcc tcgtgcccat cacccacaac gccagctacg tcgtcaccca cacccccttg 2040

ccccgcggga tcggatacaa gcttacgggc gttgacgtcc gccgcccgct gtttatcacc 2100

tatctcaccg ccacctgcga agggcacgcg cgggagattg agccgaagcg gctggtgcgc 2160

accgaaaacc ggcgcgacct cggcctcgtg ggggccgtgt ttctgcgcta caccccggcc 2220

ggggaggtca tgtcggtgct gctggtggac acggatgcca cccaacagca gctggcccag 2280

gggccggtgg cgggcacccc gaacgtgttt tccagcgacg tgccgtccgt ggccctgttg 2340

ttgttcccca acggaactgt gattcatctg ctggcctttg acacgctgcc catcgccacc 2400

atcgcccccg ggtttctggc cgcgtccgcg ctgggggtcg ttatgattac cgcggccctg 2460

gcgggcatcc ttagggtggt ccgaacgtgc gtcccatttt tgtggagacg cgaataa 2517

<210> 103

<211> 675

<212> DNA

<213> human herpesvirus 2 strain HG52

<220>

<223> NC_001798.2:9463-10137 human herpesvirus 2 strain HG52,

glycoprotein L-UL1

<400> 103

atggggttcg tctgtctgtt tgggcttgtc gttatgggag cctggggggc gtggggtggg 60

tcacaggcaa ccgaatatgt tcttcgtagt gttattgcca aagaggtggg ggacatacta 120

agagtgcctt gcatgcggac ccccgcggac gatgtttctt ggcgctacga ggccccgtcc 180

gttattgact atgcccgcat agacggaata tttcttcgct atcactgccc ggggttggac 240

acgtttttgt gggataggca cgcccagagg gcgtatctgg ttaacccctt tctctttgcg 300

gcgggatttt tggaggactt gagtcactct gtgtttccgg ccgacaccca ggaaacaacg 360

acgcgccggg ccctttataa agagatacgc gatgcgttgg gcagtcgaaa acaggccgtc 420

agccacgcac ccgtcagggc cgggtgtgta aactttgact actcacgcac tcgccgctgc 480

gtcgggcgac gcgatttacg gcctgccaac accacgtcaa cgtgggaacc gcctgtgtcg 540

tcggacgatg aagcgagctc gcagtcgaag cccctcgcca cccagccgcc cgtcctcgcc 600

ctttcgaacg cccccccacg gcgggtctcc ccgacgcgag gtcggcgccg gcatactcgc 660

ctccgacgca actag 675

<210> 104

<211> 1065

<212> DNA

<213> human herpesvirus 3

<220>

<223> NC_001348.1:114496-115560 human herpesvirus 3 genome,

glycoprotein gE

<400> 104

atgtttttaa tccaatgttt gatatcggcc gttatatttt acatacaagt gaccaacgct 60

ttgatcttca agggcgacca cgtgagcttg caagttaaca gcagtctcac gtctatcctt 120

attcccatgc aaaatgataa ttatacagag ataaaaggac agcttgtctt tattggagag 180

caactaccta ccgggacaaa ctatagcgga acactggaac tgttatacgc ggatacggtg 240

gcgttttgtt tccggtcagt acaagtaata agatacgacg gatgtccccg gattagaacg 300

agcgctttta tttcgtgtag gtacaaacat tcgtggcatt atggtaactc aacggatcgg 360

atatcaacag agccggatgc tggtgtaatg ttgaaaatta ccaaaccggg aataaatgat 420

gctggtgtgt atgtacttct tgttcggtta gaccatagca gatccaccga tggtttcatt 480

cttggtgtaa atgtatatac agcgggctcg catcacaaca ttcacggggt tatctacact 540

tctccgtctc tacagaatgg atattctaca agagcccttt ttcaacaagc tcgtttgtgt 600

gatttacccg cgacacccaa agggtccggt acctccctgt ttcaacatat gcttgatctt 660

cgtgccggta aatcgttaga ggataaccct tggttacatg aggacgttgt tacgacagaa 720

actaagtccg ttgttaagga ggggatagaa aatcacgtat atccaacgga tatgtccacg 780

ttacccgaaa agtcccttaa tgatcctcca gaaaatctac ttataattat tcctatagta 840

gcgtctgtca tgatcctcac cgccatggtt attgttattg taataagcgt taagcgacgt 900

agaattaaaa aacatccaat ttatcgccca aatacaaaaa caagaagggg catacaaaat 960

gcgacaccag aatccgatgt gatgttggag gccgccattg cacaactagc aacgattcgc 1020

gaagaatccc ccccacattc cgttgtaaac ccgtttgtta aatag 1065

<210> 105

<211> 1872

<212> DNA

<213> human herpesvirus 3

<220>

<223> NC_001348.1:115808-117679 human herpesvirus 3 genome,

glycoprotein gI

<400> 105

atggggacag ttaataaacc tgtggtgggg gtattgatgg ggttcggaat tatcacggga 60

acgttgcgta taacgaatcc ggtcagagca tccgtcttgc gatacgatga ttttcacacc 120

gatgaagaca aactggatac aaactccgta tatgagcctt actaccattc agatcatgcg 180

gagtcttcat gggtaaatcg gggagagtct tcgcgaaaag cgtacgatca taactcacct 240

tatatatggc cacgtaatga ttatgatgga tttttagaga acgcacacga acaccatggg 300

gtgtataatc agggccgtgg tatcgatagc ggggaacggt taatgcaacc cacacaaatg 360

tctgcacagg aggatcttgg ggacgatacg ggcatccacg ttatccctac gttaaacggc 420

gatgacagac ataaaattgt aaatgtggac caacgtcaat acggtgacgt gtttaaagga 480

gatcttaatc caaaacccca aggccaaaga ctcattgagg tgtcagtgga agaaaatcac 540

ccgtttactt tacgcgcacc gattcagcgg atttatggag tccggtacac cgagacttgg 600

agctttttgc cgtcattaac ctgtacggga gacgcagcgc ccgccatcca gcatatatgt 660

ttaaaacata caacatgctt tcaagacgtg gtggtggatg tggattgcgc ggaaaatact 720

aaagaggatc agttggccga aatcagttac cgttttcaag gtaagaagga agcggaccaa 780

ccgtggattg ttgtaaacac gagcacactg tttgatgaac tcgaattaga cccccccgag 840

attgaaccgg gtgtcttgaa agtacttcgg acagaaaaac aatacttggg tgtgtacatt 900

tggaacatgc gcggctccga tggtacgtct acctacgcca cgtttttggt cacctggaaa 960

ggggatgaaa aaacaagaaa ccctacgccc gcagtaactc ctcaaccaag aggggctgag 1020

tttcatatgt ggaattacca ctcgcatgta ttttcagttg gtgatacgtt tagcttggca 1080

atgcatcttc agtataagat acatgaagcg ccatttgatt tgctgttaga gtggttgtat 1140

gtccccatcg atcctacatg tcaaccaatg cggttatatt ctacgtgttt gtatcatccc 1200

aacgcacccc aatgcctctc tcatatgaat tccggttgta catttacctc gccacattta 1260

gcccagcgtg ttgcaagcac agtgtatcaa aattgtgaac atgcagataa ctacaccgca 1320

tattgtctgg gaatatctca tatggagcct agctttggtc taatcttaca cgacgggggc 1380

accacgttaa agtttgtaga tacacccgag agtttgtcgg gattatacgt ttttgtggtg 1440

tattttaacg ggcatgttga agccgtagca tacactgttg tatccacagt agatcatttt 1500

gtaaacgcaa ttgaagagcg tggatttccg ccaacggccg gtcagccacc ggcgactact 1560

aaacccaagg aaattacccc cgtaaacccc ggaacgtcac cacttctacg atatgccgca 1620

tggaccggag ggcttgcagc agtagtactt ttatgtctcg taatattttt aatctgtacg 1680

gctaaacgaa tgagggttaa agcctatagg gtagacaagt ccccgtataa ccaaagcatg 1740

tattacgctg gccttccagt ggacgatttc gaggactcgg aatctacgga tacggaagaa 1800

gagtttggta acgcgattgg agggagtcac gggggttcga gttacacggt gtatatagat 1860

aagacccggt ga 1872

<210> 106

<211> 2796

<212> DNA

<213> human herpesvirus 3

<220>

<223> NC_001348.1:56819-59614 human herpesvirus 3 genome, glycoprotein

gB

<400> 106

atgtcccctt gtggctatta ttcaaagtgg agaaacaggg atcgaccaga ataccgtcgt 60

aatctacgat tcagacgttt tttctcttct atacacccta atgcagcggc tggctccgga 120

ttcaacggac ccggcgtttt cataacctcc gttacggggg tgtggttatg ctttttatgc 180

atattttcta tgtttgttac ggcggttgtg tcggtctctc caagctcgtt ttatgagagt 240

ttacaagtag agcccacaca atcagaagat ataacccggt ctgctcatct gggcgatggt 300

gatgaaatca gagaagctat acacaagtcc caggacgccg aaacaaaacc cacgttttac 360

gtctgcccac cgccaacagg ctccacaatc gtacgattag aaccaactcg gacatgtccg 420

gattatcacc ttggtaaaaa ctttacagag ggtattgctg ttgtttataa agaaaacatt 480

gcagcgtaca agtttaaggc gacggtatat tacaaagatg ttatcgttag cacggcgtgg 540

gccggaagtt cttatacgca aattactaat agatatgcgg atagggtacc aattcccgtt 600

tcagagatca cggacaccat tgataagttt ggcaagtgtt cttctaaagc aacgtacgta 660

cgaaataacc acaaagttga agcctttaat gaggataaaa atccacagga tatgcctcta 720

atcgcatcaa aatataattc tgtgggatcc aaagcatggc atactaccaa tgacacgtac 780

atggttgccg gaacccccgg aacatatagg acgggcacgt cggtgaattg catcattgag 840

gaagttgaag ccagatcaat attcccttat gatagttttg gactttccac gggagatata 900

atatacatgt ccccgttttt tggcctacgg gatggtgcat acagagaaca ttccaattat 960

gcaatggatc gttttcacca gtttgagggt tatagacaaa gggatcttga cactagagca 1020

ttactggaac ctgcagcgcg gaacttttta gtcacgcctc atttaacggt tggttggaac 1080

tggaagccaa aacgaacgga agtttgttcg cttgtcaagt ggcgtgaggt tgaagacgta 1140

gttcgcgatg agtatgcaca caattttcgc tttacaatga aaacactttc taccacgttt 1200

ataagtgaaa caaacgagtt taatcttaac caaatccatc tcagtcaatg tgtaaaggag 1260

gaagcccggg ctattattaa ccggatctat acaaccagat acaactcatc tcatgttaga 1320

accggggata tccagaccta ccttgccaga ggggggtttg ttgtggtgtt tcaacccctg 1380

ctgagcaatt ccctcgcccg tctctatctc caagaattgg tccgtgaaaa cactaatcat 1440

tcaccacaaa aacacccgac tcgaaatacc agatcccgac gaagcgtgcc agttgagttg 1500

cgtgccaata gaacaataac aaccacctca tcggtggaat ttgctatgct ccagtttaca 1560

tatgaccaca ttcaagagca tgttaatgaa atgttggcac gtatctcctc gtcgtggtgc 1620

cagctacaaa atcgcgaacg cgccctttgg agcggactat ttccaattaa cccaagtgct 1680

ttagcgagca ccattttgga tcaacgtgtt aaagctcgta ttctcggcga cgttatctcc 1740

gtttctaatt gtccagaact gggatcagat acacgcatta tacttcaaaa ctctatgagg 1800

gtatctggta gtactacgcg ttgttatagc cgtcctttaa tttcaatagt tagtttaaat 1860

gggtccggga cggtggaggg ccagcttgga acagataacg agttaattat gtccagagat 1920

ctgttagaac catgcgtggc taatcacaag cgatattttc tatttgggca tcactacgta 1980

tattatgagg attatcgtta cgtccgtgaa atcgcagtcc atgatgtggg aatgattagc 2040

acttacgtag atttaaactt aacacttctt aaagatagag agtttatgcc gctgcaagta 2100

tatacaagag acgagctgcg ggatacagga ttactagact acagtgaaat tcaacgccga 2160

aatcaaatgc attcgctgcg tttttatgac atagacaagg ttgtgcaata tgatagcgga 2220

acggccatta tgcagggcat ggctcagttt ttccagggac ttgggaccgc gggccaggcc 2280

gttggacatg tggttcttgg ggccacggga gcgctgcttt ccaccgtaca cggatttacc 2340

acgtttttat ctaacccatt tggggcattg gccgtgggat tattggtttt ggcgggactg 2400

gtagcggcct tttttgcgta ccggtacgtg cttaaactta aaacaagccc gatgaaggca 2460

ttatatccac tcacaaccaa ggggttaaaa cagttaccgg aaggaatgga tccctttgcc 2520

gagaaaccca acgctactga taccccaata gaagaaattg gcgactcaca aaacactgaa 2580

ccgtcggtaa atagcgggtt tgatcccgat aaatttcgag aagcccagga aatgattaaa 2640

tatatgacgt tagtatctgc ggctgagcgc caagaatcta aagcccgcaa aaaaaataag 2700

actagcgccc ttttaacttc acgtcttacc ggccttgctt tacgaaatcg ccgaggatac 2760

tcccgtgttc gcaccgagaa tgtaacgggg gtgtaa 2796

<210> 107

<211> 2526

<212> DNA

<213> human herpesvirus 3

<220>

<223> NC_001348.1:66074-68599 human herpesvirus 3 genome, glycoprotein

gH orf37

<400> 107

atgtttgcgc tagttttagc ggtggtaatt cttcctcttt ggaccacggc taataaatct 60

tacgtaacac caacccctgc gactcgctct atcggacata tgtctgctct tctacgagaa 120

tattccgacc gtaatatgtc tctgaaatta gaagcctttt atcctactgg tttcgatgaa 180

gaactcatta aatcacttca ctggggaaat gatagaaaac acgttttctt ggttattgtt 240

aaggttaacc ctacaacaca cgaaggagac gtcgggctgg ttatatttcc aaaatacttg 300

ttatcgccat accatttcaa agcagaacat cgagcaccgt ttcctgctgg acgttttgga 360

tttcttagtc accctgtgac acccgacgtg agcttctttg acagttcgtt tgcgccgtat 420

ttaactacgc aacatcttgt tgcgtttact acgttcccac caaaccccct tgtatggcat 480

ttggaaagag ctgagaccgc agcaactgca gaaaggccgt ttggggtaag tcttttaccc 540

gctcgcccaa cagtccccaa gaatactatt ctggaacata aagcgcattt tgctacatgg 600

gatgcccttg cccgacatac ttttttttct gccgaagcaa ttatcaccaa ctcaacgttg 660

agaatacacg ttcccctttt tgggtcggta tggccaattc gatactgggc caccggttcg 720

gtgcttctca caagcgactc gggtcgtgtg gaagtaaata ttggtgtagg atttatgagc 780

tcgctcattt ctttatcctc tggaccaccg atagaattaa ttgttgtacc acatacagta 840

aaactgaacg cggttacaag cgacaccaca tggttccagc taaatccacc gggtccggat 900

ccggggccat cttatcgagt ttatttactt ggacgtgggt tggatatgaa tttttcaaag 960

catgctacgg tcgatatatg cgcatatccc gaagagagtt tggattaccg ctatcattta 1020

tccatggccc acacggaggc tctgcggatg acaacgaagg cggatcaaca tgacataaac 1080

gaggaaagct attaccatat cgccgcaaga atagccacat caatttttgc gttgtcggaa 1140

atgggccgta ccacagaata ttttctgtta gatgagatcg tagatgttca gtatcaatta 1200

aaattcctta attacatttt aatgcggata ggagcaggag ctcatcccaa cactatatcc 1260

ggaacctcgg atctgatctt tgccgatcca tcgcagcttc atgacgaact ttcacttctt 1320

tttggtcagg taaaacccgc aaatgtcgat tattttattt catatgatga agcccgtgat 1380

caactaaaga ccgcatacgc gctttcccgt ggtcaagacc atgtgaatgc actttctctc 1440

gccaggcgtg ttataatgag catatacaag gggctgcttg tgaagcaaaa tttaaatgct 1500

acagagaggc aggctttatt ttttgcctca atgattttat taaatttccg cgaaggacta 1560

gaaaattcat ctcgggtatt agacggtcgc acaactttgc ttttaatgac atccatgtgt 1620

acggcagctc acgccacgca agcagcactt aacatacaag aaggcctggc atacttaaat 1680

ccttcaaaac acatgtttac aataccaaac gtatacagtc cttgtatggg ttcccttcgt 1740

acagacctca cggaagagat tcatgttatg aatctcctgt cggcaatacc aacacgccca 1800

ggacttaacg aggtattgca tacccaacta gacgaatctg aaatattcga cgcggcattt 1860

aaaaccatga tgatttttac cacatggact gccaaagatt tgcatatact ccacacccat 1920

gtaccagaag tatttacgtg tcaagatgca gccgcgcgta acggagaata tgtgctcatt 1980

cttccagctg tccagggaca cagttatgtg attacacgaa acaaacctca aaggggtttg 2040

gtatattccc tggcagatgt ggatgtatat aaccccatat ccgttgttta tttaagcagg 2100

gatacttgcg tgtctgaaca tggtgtcata gagacggtcg cactgcccca tccggacaat 2160

ttaaaagaat gtttgtattg cggaagtgtt tttcttaggt atctaaccac gggggcgatt 2220

atggatataa ttattattga cagcaaagat acagaacgac aactagccgc tatgggaaac 2280

tccacaattc cacccttcaa tccagacatg cacggggatg actctaaggc tgtgttgttg 2340

tttccaaacg gaactgtggt aacgcttcta ggattcgaac gacgacaagc catacgaatg 2400

tcgggacaat accttggggc ctctttagga ggggcgtttc tggcggtagt ggggtttggt 2460

attatcggat ggatgttatg tggaaattcc cgccttcgag aatataataa aatacctctg 2520

acataa 2526

<210> 108

<211> 480

<212> DNA

<213> human herpesvirus 3

<220>

<223> NC_001348.1:c101649-101170 human herpesvirus 3 genome,

glycoprotein gL, ORF60

<400> 108

atggcatcac ataaatggtt actgcagata gtttttttaa aaactatcac aatcgcgtat 60

tgtcttcatc tccaagacga cactccgttg ttttttggag ccaaaccgct atcggatgtg 120

agtttgatta taacggaacc gtgcgtgtca tcggtatatg aggcgtggga ctatgcggca 180

cccccggtat caaacctcag cgaggcgcta tcgggaatcg tggttaagac aaaatgtcca 240

gtaccggaag ttatactttg gtttaaagac aaacaaatgg cgtactggac aaatccatac 300

gtcaccttaa aggggctggc acaatctgtt ggtgaagaac ataaaagcgg ggacatacgc 360

gatgctttgt tggatgccct ttccggtgta tgggtagact ctactccatc ttccacaaat 420

atcccggaaa atggatgtgt ctggggagcc gaccgtttgt tccaacgcgt atgccaatga 480

<210> 109

<211> 13

<212> RNA

<213> artificial sequence

<220>

<223> Kozak consensus sequences

<400> 109

gccgccrcca ugg 13

<210> 110

<211> 10

<212> DNA

<213> human herpesvirus 2 strain HG52

<220>

<223> HSV2 Strain HG52 gH Kozak sequence

<400> 110

acgaccatgg 10

<210> 111

<211> 31

<212> PRT

<213> human herpesvirus 6A

<220>

<223> HHV 6A-mutant

<400> 111

Tyr Phe Ala Arg Gly Pro Leu Trp Leu Tyr Ser Thr Ser Ala Ser Leu

1 5 10 15

Asn Cys Ile Val Thr Glu Ala Thr Ala Lys Ala Lys Tyr Pro Phe

20 25 30

<210> 112

<211> 31

<212> PRT

<213> human herpesvirus 6A

<220>

<223> HHV6A-wt

<400> 112

Tyr Phe Ala Arg Gly Pro Leu Trp Leu Tyr Ser Thr Ser Thr Ser Leu

1 5 10 15

Asn Cys Ile Val Thr Glu Ala Thr Ala Lys Ala Lys Tyr Pro Phe

20 25 30

<210> 113

<211> 31

<212> PRT

<213> human herpesvirus 6B

<220>

<223> HHV6B

<400> 113

Tyr Phe Ala Arg Gly Pro Leu Trp Leu Tyr Ser Thr Ser Thr Ser Leu

1 5 10 15

Asn Cys Ile Val Thr Glu Ala Thr Ala Lys Ala Lys Tyr Pro Phe

20 25 30

<210> 114

<211> 31

<212> PRT

<213> human herpesvirus 5

<220>

<223> HMCV

<400> 114

Trp His Ser Arg Gly Ser Thr Trp Leu Tyr Arg Glu Thr Cys Asn Leu

1 5 10 15

Asn Cys Met Val Thr Ile Thr Thr Ala Arg Ser Lys Tyr Pro Tyr

20 25 30

<210> 115

<211> 32

<212> PRT

<213> human herpesvirus 4

<220>

<223> EBV1/2

<400> 115

Tyr Asp Ala Pro Gly Trp Leu Ile Trp Thr Tyr Arg Thr Arg Thr Thr

1 5 10 15

Val Asn Cys Leu Ile Thr Asp Met Met Ala Lys Ser Asn Ser Pro Phe

20 25 30

<210> 116

<211> 32

<212> PRT

<213> human herpesvirus 8

<220>

<223> KSHV

<400> 116

Tyr Ala Glu Pro Gly Trp Phe Pro Gly Ile Tyr Arg Val Arg Thr Thr

1 5 10 15

Val Asn Cys Glu Ile Val Asp Met Ile Ala Arg Ser Ala Glu Pro Tyr

20 25 30

<210> 117

<211> 31

<212> PRT

<213> human herpesvirus 3

<220>

<223> VZV

<400> 117

Tyr Met Val Ala Gly Thr Pro Gly Thr Tyr Arg Thr Gly Thr Ser Val

1 5 10 15

Asn Cys Ile Ile Glu Glu Val Glu Ala Arg Ser Ile Phe Pro Tyr

20 25 30

<210> 118

<211> 31

<212> PRT

<213> human herpesvirus 1

<220>

<223> HSV1

<400> 118

Tyr Asn Pro Ser Arg Val Glu Ala Phe His Arg Tyr Gly Thr Thr Val

1 5 10 15

Asn Cys Ile Val Glu Glu Val Asp Ala Arg Ser Val Tyr Pro Tyr

20 25 30

<210> 119

<211> 31

<212> PRT

<213> human herpesvirus 3

<220>

<223> HSV2

<400> 119

Tyr Asn Pro Ser Arg Val Glu Ala Phe His Arg Tyr Gly Thr Thr Val

1 5 10 15

Asn Cys Ile Val Glu Glu Val Asp Ala Arg Ser Val Tyr Pro Tyr

20 25 30

<210> 120

<211> 31

<212> PRT

<213> artificial sequence

<220>

<223> HSV2 mutant

<400> 120

Tyr Asn Pro Ser Arg Val Glu Ala Phe His Arg Tyr Gly Ala Thr Val

1 5 10 15

Asn Cys Ile Val Glu Glu Val Asp Ala Arg Ser Val Tyr Pro Tyr

20 25 30

<210> 121

<211> 60

<212> PRT

<213> human herpesvirus 2

<220>

<223> HSV2 52Q-P

<400> 121

Met Gly Arg Leu Thr Ser Gly Val Gly Thr Ala Ala Leu Leu Val Val

1 5 10 15

Ala Val Gly Leu Arg Val Val Cys Ala Lys Tyr Ala Leu Ala Asp Pro

20 25 30

Ser Leu Lys Met Ala Asp Pro Asn Arg Phe Arg Gly Lys Asn Leu Pro

35 40 45

Val Leu Asp Gln Leu Thr Asp Pro Pro Gly Val Lys

50 55 60

<210> 122

<211> 60

<212> PRT

<213> human herpesvirus 1

<220>

<223> HSV1

<400> 122

Met Gly Gly Ala Ala Ala Arg Leu Gly Ala Val Ile Leu Phe Val Val

1 5 10 15

Ile Val Gly Leu His Gly Val Arg Gly Lys Tyr Ala Leu Val Asp Ala

20 25 30

Ser Leu Lys Met Ala Asp Pro Asn Arg Phe Arg Gly Lys Asp Leu Pro

35 40 45

Val Leu Asp Gln Leu Thr Asp Pro Pro Gly Val Arg

50 55 60

<210> 123

<211> 23

<212> PRT

<213> human herpesvirus 3

<220>

<223> VSV

<400> 123

Lys Arg Tyr Phe Leu Phe Gly His His Tyr Val Tyr Tyr Glu Asp Tyr

1 5 10 15

Arg Tyr Val Arg Glu Ile Ala

20

<210> 124

<211> 23

<212> PRT

<213> human herpesvirus 1

<220>

<223> HSV1

<400> 124

Arg Arg Tyr Phe Thr Phe Gly Gly Gly Tyr Val Tyr Phe Glu Glu Tyr

1 5 10 15

Ala Tyr Ser His Gln Leu Ser

20

<210> 125

<211> 23

<212> PRT

<213> human herpesvirus 2

<220>

<223> HSV2

<400> 125

Arg Arg Tyr Phe Ile Phe Gly Gly Gly Tyr Val Tyr Phe Glu Glu Tyr

1 5 10 15

Ala Tyr Ser His Gln Leu Ser

20

<210> 126

<211> 23

<212> PRT

<213> human gamma herpes virus 4

<220>

<223> EBV2

<400> 126

Gln Tyr Tyr Phe Gln Ser Gly Asn Glu Ile His Val Tyr Asn Asp Tyr

1 5 10 15

His His Phe Lys Thr Ile Glu

20

<210> 127

<211> 23

<212> PRT

<213> human herpesvirus 8

<220>

<223> KSHV

<400> 127

Glu His Tyr Phe Ile Thr Arg Asn Glu Thr Leu Val Tyr Lys Asp Tyr

1 5 10 15

Ala Tyr Leu Arg Thr Ile Asn

20

<210> 128

<211> 23

<212> PRT

<213> human herpesvirus 5

<220>

<223> HCMV

<400> 128

Leu Lys Ile Phe Ile Ala Gly Asn Ser Ala Tyr Glu Tyr Val Asp Tyr

1 5 10 15

Leu Phe Lys Arg Met Ile Asp

20

<210> 129

<211> 25

<212> PRT

<213> human herpesvirus 6A

<220>

<223> HHV6A

<400> 129

Thr Lys Ile Phe Leu Ser Gly Asn His Ala His Val Tyr Thr Asp Tyr

1 5 10 15

Thr His Thr Asn Ser Thr Pro Ile Glu

20 25

<210> 130

<211> 25

<212> PRT

<213> human herpesvirus 6B

<400> 130

Thr Lys Ile Phe Leu Ser Gly Asn His Ala His Val Tyr Thr Asp Tyr

1 5 10 15

Thr His Thr Asn Ser Thr Pro Ile Glu

20 25

<210> 131

<211> 26

<212> PRT

<213> human herpesvirus 7

<220>

<223> HHV7

<400> 131

Thr Lys Ile Phe Leu Ser Gly Lys Phe Ala His Ile Phe Lys Asp Tyr

1 5 10 15

Thr Tyr Val Asn Ser Ser Leu Ile Thr Glu

20 25

<210> 132

<211> 2715

<212> DNA

<213> artificial sequence

<220>

<223> HSV1 Strain 17 domain III SNP His516Pro 1547A-C

<400> 132

atgcgccagg gcgcccccgc gcgggggcgc cggtggttcg tcgtatgggc gctcttgggg 60

ttgacgctgg gggtcctggt ggcgtcggcg gctccgagtt cccccggcac gcctggggtc 120

gcggccgcga cccaggcggc gaacgggggc cctgccactc cggcgccgcc cgcccctggc 180

gcccccccaa cgggggaccc gaaaccgaag aagaacaaaa aaccgaaacc cccaaagccg 240

ccgcgccccg ccggcgacaa cgcgaccgtc gccgcgggcc acgccaccct gcgcgagcac 300

ctgcgggaca tcaaggcgga gaacaccgat gcaaactttt acgtgtgccc accccccacg 360

ggcgccacgg tggtgcagtt cgagcagccg cgccgctgcc cgacccggcc cgagggtcag 420

aactacacgg agggcatcgc ggtggtcttc aaggagaaca tcgccccgta caagttcaag 480

gccaccatgt actacaaaga cgtcaccgtt tcgcaggtgt ggttcggcca ccgctactcc 540

cagtttatgg ggatctttga ggaccgcgcc cccgtcccct tcgaggaggt gatcgacaag 600

atcaacgcca agggggtctg tcggtccacg gccaagtacg tgcgcaacaa cctggagacc 660

accgcgtttc accgggacga ccacgagacc gacatggagc tgaaaccggc caacgccgcg 720

acccgcacga gccggggctg gcacaccacc gacctcaagt acaacccctc gcgggtggag 780

gcgttccacc ggtacgggac gacggtaaac tgcatcgtcg aggaggtgga cgcgcgctcg 840

gtgtacccgt acgacgagtt tgtgttggcg actggcgact ttgtgtacat gtccccgttt 900

tacggctacc gggaggggtc gcacaccgaa cacaccagct acgccgccga ccgcttcaag 960

caggtcgacg gcttctacgc gcgcgacctc accaccaagg cccgggccac ggcgccgacc 1020

acccggaacc tgctcacgac ccccaagttc accgtggcct gggactgggt gccaaagcgc 1080

ccgtcggtct gcaccatgac caagtggcag gaggtggacg agatgctgcg ctccgagtac 1140

ggcggctcct tccgattctc ttccgacgcc atatccacca ccttcaccac caacctgacc 1200

gagtacccgc tctcgcgcgt ggacctgggg gactgcatcg gcaaggacgc ccgcgacgcc 1260

atggaccgca tcttcgcccg caggtacaac gcgacgcaca tcaaggtggg ccagccgcag 1320

tactacctgg ccaatggggg ctttctgatc gcgtaccagc cccttctcag caacacgctc 1380

gcggagctgt acgtgcggga acacctccgc gagcagagcc gcaagccccc aaaccccacg 1440

cccccgccgc ccggggccag cgccaacgcg tccgtggagc gcatcaagac cacctcctcc 1500

atcgagttcg ccaggctgca gtttacgtac aaccacatac agcgccctgt caacgatatg 1560

ttgggccgcg ttgccatcgc gtggtgcgag ctgcagaatc acgagctgac cctgtggaac 1620

gaggcccgca agctgaaccc caacgccatc gcctcggcca ccgtgggccg gcgggtgagc 1680

gcgcggatgc tcggcgacgt gatggccgtc tccacgtgcg tgccggtcgc cgcggacaac 1740

gtgatcgtcc aaaactcgat gcgcatcagc tcgcggcccg gggcctgcta cagccgcccc 1800

ctggtcagct ttcggtacga agaccagggc ccgttggtcg aggggcagct gggggagaac 1860

aacgagctgc ggctgacgcg cgatgcgatc gagccgtgca ccgtgggaca ccggcgctac 1920

ttcaccttcg gtgggggcta cgtgtacttc gaggagtacg cgtactccca ccagctgagc 1980

cgcgccgaca tcaccaccgt cagcaccttc atcgacctca acatcaccat gctggaggat 2040

cacgagtttg tccccctgga ggtgtacacc cgccacgaga tcaaggacag cggcctgctg 2100

gactacacgg aggtccagcg ccgcaaccag ctgcacgacc tgcgcttcgc cgacatcgac 2160

acggtcatcc acgccgacgc caacgccgcc atgtttgcgg gcctgggcgc gttcttcgag 2220

gggatgggcg acctggggcg cgcggtcggc aaggtggtga tgggcatcgt gggcggcgtg 2280

gtatcggccg tgtcgggcgt gtcctccttc atgtccaacc cctttggggc gctggccgtg 2340

ggtctgttgg tcctggccgg cctggcggcg gccttcttcg cctttcgcta cgtcatgcgg 2400

ctgcagagca accccatgaa ggccctgtac ccgctaacca ccaaggagct caagaacccc 2460

accaacccgg acgcgtccgg ggagggcgag gagggcggcg actttgacga ggccaagcta 2520

gccgaggccc gggagatgat acggtacatg gccctggtgt ctgccatgga gcgcacggaa 2580

cacaaggcca agaagaaggg cacgagcgcg ctgctcagcg ccaaggtcac cgacatggtc 2640

atgcgcaagc gccgcaacac caactacacc caagttccca acaaagacgg tgacgccgac 2700

gaggacgacc tgtga 2715

<210> 133

<211> 2715

<212> DNA

<213> artificial sequence

<220>

<223> HSV2 strain HG52 gB2 domain III SNP encoding His513-Pro SNP 1538

A-C

<400> 133

atgcgcgggg ggggcttgat ttgcgcgctg gtcgtggggg cgctggtggc cgcggtggcg 60

tcggcggccc cggcggcccc ggcggccccc cgcgcctcgg gcggcgtggc cgcgaccgtc 120

gcggcgaacg ggggtcccgc ctcccggccg ccccccgtcc cgagccccgc gaccaccaag 180

gcccggaagc ggaaaaccaa aaagccgccc aagcggcccg aggcgacccc gccccccgac 240

gccaacgcga ccgtcgccgc cggccacgcc acgctgcgcg cgcacctgcg ggaaatcaag 300

gtcgagaacg ccgatgccca gttttacgtg tgcccgcccc cgacgggcgc cacggtggtg 360

cagtttgagc agccgcgccg ctgcccgacg cgcccggagg ggcagaacta cacggagggc 420

atcgcggtgg tcttcaagga gaacatcgcc ccgtacaaat tcaaggccac catgtactac 480

aaagacgtga ccgtgtcgca ggtgtggttc ggccaccgct actcccagtt tatggggata 540

ttcgaggacc gcgcccccgt tcccttcgag gaggtgatcg acaagattaa cgccaagggg 600

gtctgccgct ccacggccaa gtacgtgcgg aacaacatgg agaccaccgc gtttcaccgg 660

gacgaccacg agaccgacat ggagctcaag ccggcgaagg tcgccacgcg cacgagccgg 720

gggtggcaca ccaccgacct caagtacaac ccctcgcggg tggaggcgtt ccatcggtac 780

ggcacgacgg tcaactgcat cgtcgaggag gtggacgcgc ggtcggtgta cccgtacgat 840

gagtttgtgc tggcgacggg cgactttgtg tacatgtccc cgttttacgg ctaccgggag 900

gggtcgcaca ccgagcacac cagctacgcc gccgaccgct tcaagcaggt cgacggcttc 960

tacgcgcgcg acctcaccac gaaggcccgg gccacgtcgc cgacgacccg caacttgctg 1020

acgaccccca agtttaccgt ggcctgggac tgggtgccga agcgaccggc ggtctgcacc 1080

atgaccaagt ggcaggaggt ggacgagatg ctccgcgccg agtacggcgg ctccttccgc 1140

ttctcctccg acgccatctc gaccaccttc accaccaacc tgaccgagta ctcgctctcg 1200

cgcgtcgacc tgggcgactg catcggccgg gatgcccgcg aggccatcga ccgcatgttt 1260

gcgcgcaagt acaacgccac gcacatcaag gtgggccagc cgcagtacta cctggccacg 1320

gggggcttcc tcatcgcgta ccagcccctc ctcagcaaca cgctcgccga gctgtacgtg 1380

cgggagtaca tgcgggagca ggaccgcaag ccccggaatg ccacgcccgc gccactgcgg 1440

gaggcgccca gcgccaacgc gtccgtggag cgcatcaaga ccacctcctc gatcgagttc 1500

gcccggctgc agtttacgta taaccacata cagcgccccg tgaacgacat gctggggcgc 1560

atcgccgtcg cgtggtgcga gctgcagaac cacgagctga ctctctggaa cgaggcccgc 1620

aagctcaacc ccaacgccat cgcctccgcc accgtcggcc ggcgggtgag cgcgcgcatg 1680

ctcggagacg tcatggccgt ctccacgtgc gtgcccgtcg ccccggacaa cgtgatcgtg 1740

cagaactcga tgcgcgtcag ctcgcggccg gggacgtgct acagccgccc cctggtcagc 1800

tttcggtacg aagaccaggg cccgctgatc gaggggcagc tgggcgagaa caacgagctg 1860

cgcctcaccc gcgacgcgct cgagccgtgc accgtgggcc accggcgcta cttcatcttc 1920

ggcgggggct acgtgtactt cgaggagtac gcgtactctc accagctgag tcgcgccgac 1980

gtcaccaccg tcagcacctt catcgacctg aacatcacca tgctggagga ccacgagttt 2040

gtgcccctgg aggtctacac gcgccacgag atcaaggaca gcggcctgct ggactacacg 2100

gaggtccagc gccgcaacca gctgcacgac ctgcgctttg ccgacatcga cacggtcatc 2160

cgcgccgacg ccaacgccgc catgttcgcg gggctgtgcg cgttcttcga ggggatgggg 2220

gacttggggc gcgcggtcgg caaggtagtc atgggagtag tggggggcgt ggtgtcggcc 2280

gtctcgggcg tgtcctcctt tatgtccaac cccttcgggg cgcttgccgt ggggctgctg 2340

gtcctggccg gcctggtcgc ggccttcttc gccttccgct acgtcctgca actgcaacgc 2400

aatcccatga aggccctgta tccgctcacc accaaggaac tcaagacttc cgaccccggg 2460

ggcgtgggcg gggaggggga ggaaggcgcg gaggggggcg ggtttgacga ggccaagttg 2520

gccgaggccc gagaaatgat ccgatatatg gctttggtgt cggccatgga gcgcacggaa 2580

cacaaggcca gaaagaaggg cacgagcgcc ctgctcagct ccaaggtcac caacatggtt 2640

ctgcgcaagc gcaacaaagc caggtactct ccgctccaca acgaggacga ggccggagac 2700

gaagacgagc tctaa 2715

<210> 134

<211> 2796

<212> DNA

<213> artificial sequence

<220>

<223> Dumas SNP of the VZV gB3 strain encoding His526Pro 1580A-C

<400> 134

atgtcccctt gtggctatta ttcaaagtgg agaaacaggg atcgaccaga ataccgtcgt 60

aatctacgat tcagacgttt tttctcttct atacacccta atgcagcggc tggctccgga 120

ttcaacggac ccggcgtttt cataacctcc gttacggggg tgtggttatg ctttttatgc 180

atattttcta tgtttgttac ggcggttgtg tcggtctctc caagctcgtt ttatgagagt 240

ttacaagtag agcccacaca atcagaagat ataacccggt ctgctcatct gggcgatggt 300

gatgaaatca gagaagctat acacaagtcc caggacgccg aaacaaaacc cacgttttac 360

gtctgcccac cgccaacagg ctccacaatc gtacgattag aaccaactcg gacatgtccg 420

gattatcacc ttggtaaaaa ctttacagag ggtattgctg ttgtttataa agaaaacatt 480

gcagcgtaca agtttaaggc gacggtatat tacaaagatg ttatcgttag cacggcgtgg 540

gccggaagtt cttatacgca aattactaat agatatgcgg atagggtacc aattcccgtt 600

tcagagatca cggacaccat tgataagttt ggcaagtgtt cttctaaagc aacgtacgta 660

cgaaataacc acaaagttga agcctttaat gaggataaaa atccacagga tatgcctcta 720

atcgcatcaa aatataattc tgtgggatcc aaagcatggc atactaccaa tgacacgtac 780

atggttgccg gaacccccgg aacatatagg acgggcacgt cggtgaattg catcattgag 840

gaagttgaag ccagatcaat attcccttat gatagttttg gactttccac gggagatata 900

atatacatgt ccccgttttt tggcctacgg gatggtgcat acagagaaca ttccaattat 960

gcaatggatc gttttcacca gtttgagggt tatagacaaa gggatcttga cactagagca 1020

ttactggaac ctgcagcgcg gaacttttta gtcacgcctc atttaacggt tggttggaac 1080

tggaagccaa aacgaacgga agtttgttcg cttgtcaagt ggcgtgaggt tgaagacgta 1140

gttcgcgatg agtatgcaca caattttcgc tttacaatga aaacactttc taccacgttt 1200

ataagtgaaa caaacgagtt taatcttaac caaatccatc tcagtcaatg tgtaaaggag 1260

gaagcccggg ctattattaa ccggatctat acaaccagat acaactcatc tcatgttaga 1320

accggggata tccagaccta ccttgccaga ggggggtttg ttgtggtgtt tcaacccctg 1380

ctgagcaatt ccctcgcccg tctctatctc caagaattgg tccgtgaaaa cactaatcat 1440

tcaccacaaa aacacccgac tcgaaatacc agatcccgac gaagcgtgcc agttgagttg 1500

cgtgccaata gaacaataac aaccacctca tcggtggaat ttgctatgct ccagtttaca 1560

tatgaccaca ttcaagagcc tgttaatgaa atgttggcac gtatctcctc gtcgtggtgc 1620

cagctacaaa atcgcgaacg cgccctttgg agcggactat ttccaattaa cccaagtgct 1680

ttagcgagca ccattttgga tcaacgtgtt aaagctcgta ttctcggcga cgttatctcc 1740

gtttctaatt gtccagaact gggatcagat acacgcatta tacttcaaaa ctctatgagg 1800

gtatctggta gtactacgcg ttgttatagc cgtcctttaa tttcaatagt tagtttaaat 1860

gggtccggga cggtggaggg ccagcttgga acagataacg agttaattat gtccagagat 1920

ctgttagaac catgcgtggc taatcacaag cgatattttc tatttgggca tcactacgta 1980

tattatgagg attatcgtta cgtccgtgaa atcgcagtcc atgatgtggg aatgattagc 2040

acttacgtag atttaaactt aacacttctt aaagatagag agtttatgcc gctgcaagta 2100

tatacaagag acgagctgcg ggatacagga ttactagact acagtgaaat tcaacgccga 2160

aatcaaatgc attcgctgcg tttttatgac atagacaagg ttgtgcaata tgatagcgga 2220

acggccatta tgcagggcat ggctcagttt ttccagggac ttgggaccgc gggccaggcc 2280

gttggacatg tggttcttgg ggccacggga gcgctgcttt ccaccgtaca cggatttacc 2340

acgtttttat ctaacccatt tggggcattg gccgtgggat tattggtttt ggcgggactg 2400

gtagcggcct tttttgcgta ccggtacgtg cttaaactta aaacaagccc gatgaaggca 2460

ttatatccac tcacaaccaa ggggttaaaa cagttaccgg aaggaatgga tccctttgcc 2520

gagaaaccca acgctactga taccccaata gaagaaattg gcgactcaca aaacactgaa 2580

ccgtcggtaa atagcgggtt tgatcccgat aaatttcgag aagcccagga aatgattaaa 2640

tatatgacgt tagtatctgc ggctgagcgc caagaatcta aagcccgcaa aaaaaataag 2700

actagcgccc ttttaacttc acgtcttacc ggccttgctt tacgaaatcg ccgaggatac 2760

tcccgtgttc gcaccgagaa tgtaacgggg gtgtaa 2796

<210> 135

<211> 207

<212> DNA

<213> human herpesvirus 6A

<220>

<223> human chromosomal integration with Kozak locus

Coding region of the iciU83A-N cDNA of iciHHV-6A

<400> 135

gtcgaaatgt ccattcggct ttttattggt ttcttttata cggcatatat tggtatggct 60

atcggattta tatgtagttc ccccgatgcg gagctgtttt ccgaaaaatc acgtatttcg 120

tcttctgtct tgttaggatg tttgttgtgt tgcatggatt ggtccgctgc cgtacccgtc 180

tggtttggag cagggctcga tgtgtga 207

<210> 136

<211> 66

<212> PRT

<213> human herpesvirus 6A

<220>

<223> integration by human chromosome

iciU83A-N polypeptide encoded by iciHHV-6A

<400> 136

Met Ser Ile Arg Leu Phe Ile Gly Phe Phe Tyr Thr Ala Tyr Ile Gly

1 5 10 15

Met Ala Ile Gly Phe Ile Cys Ser Ser Pro Asp Ala Glu Leu Phe Ser

20 25 30

Glu Lys Ser Arg Ile Ser Ser Ser Val Leu Leu Gly Cys Leu Leu Cys

35 40 45

Cys Met Asp Trp Ser Ala Ala Val Pro Val Trp Phe Gly Ala Gly Leu

50 55 60

Asp Val

65

Claims

1. A pharmaceutical composition comprising one or more nucleic acid molecules comprising a plurality of immunogenic coding regions that collectively encode a plurality of herpes virus polypeptides, wherein the one or more nucleic acid molecules are capable of expressing the plurality of herpes virus polypeptides when introduced into a vertebrate cell, wherein each of the plurality of immunogenic coding regions has at least 90% sequence identity to a native coding region of a corresponding native full length herpes virus polypeptide from the same herpes virus species, wherein the plurality of herpes virus polypeptides are:

2. The pharmaceutical composition of claim 1, wherein each of the plurality of immunogen encoding regions has substantially the same codon usage, cpG bias and/or g+c content as the codon usage, cpG bias and/or g+c content of the native encoding region of the corresponding native full-length herpesvirus polypeptide.

3. The pharmaceutical composition of claim 1 or 2, wherein each of the plurality of immunogen encoding regions comprises a Kozak sequence capable of allowing the herpesvirus polypeptide to initiate translation in the vertebrate cell with an efficiency that is substantially the same as the efficiency with which the Kozak sequence of the native encoding region of the corresponding native full-length herpesvirus polypeptide allows translation to be initiated in the vertebrate cell, such as wherein the Kozak sequence of each of the plurality of immunogen encoding regions is the same as the Kozak sequence of the native encoding region of the corresponding native full-length herpesvirus polypeptide.

4. The pharmaceutical composition according to any one of the preceding claims, wherein each of the immunogen encoding regions is operably linked to a 3 'untranslated region that allows the extent of mRNA stability of the immunogen encoding region or transcript thereof to be substantially the same, such as by comprising the same 3' polyadenylation sequence.

5. The pharmaceutical composition according to any one of the preceding claims, wherein the one or more nucleic acid molecules are deoxyribonucleic acid (DNA) polynucleotides, such as plasmid expression vectors or viral vectors; or ribonucleic acid (RNA) polynucleotides, such as viral vectors.

6. The pharmaceutical composition of claim 5, wherein the one or more nucleic acid molecules are deoxyribonucleic acid (DNA) polynucleotides and each of the immunogen encoding regions is operably linked to a 5' promoter, wherein each encoding region operably linked to a 5' promoter is capable of simultaneous gene expression in the vertebrate cell, such as by virtue of each encoding region being linked to the same 5' promoter.

7. The pharmaceutical composition according to any of the preceding claims, wherein the gB polypeptide encoded by the immunogenic coding region of gB comprises a mutation that stabilizes the gB polypeptide to a trimer in a fusion construct, such as a mutation in fusion related domain I, such as a substitution at position corresponding to position 262 of SEQ ID NO 9, such as wherein the substitution is a non-conservative substitution; or a substitution at a position corresponding to position 267 of SEQ ID 91, 273 of SEQ ID 92, 202 of SEQ ID 93, 202 of SEQ ID 94, 246 of SEQ ID 95, 193 of SEQ ID 97, 190 of SEQ ID 98, 218 of SEQ ID 99, such as wherein the substitution is a non-conservative substitution.

8. The pharmaceutical composition according to any one of the preceding claims, wherein the gB polypeptide encoded by the immunogenic coding region of gB comprises a mutation in the trimer that stabilizes gB in the pre-fusion configuration, such as a mutation in gB domain III and/or IV, such as a substitution at a position corresponding to one or more of the substitutions in the encoded polypeptides of SEQ ID 67 to 90 or 132 to 134; or wherein the gD polypeptide encoded by said immunogen encoding region of gD comprises a mutation that reduces interaction with HVEM receptors, such as a substitution at a position corresponding to position 52 of SEQ ID 64 or SEQ ID 65.

9. The pharmaceutical composition of any one of the preceding claims, wherein each of the plurality of immunogen encoding regions is identical to the native encoding region of the corresponding native full-length herpesvirus polypeptide; or at least 95% sequence identity, such as at least 97% sequence identity, at least 99% sequence identity, at least 99.5% sequence identity, or 100% sequence identity, to a coding region of a variant gB polypeptide which differs from the native coding region of the corresponding native full-length gB polypeptide only by a codon corresponding to position 262 of SEQ ID NO 9 in the encoded variant gB polypeptide.

10. The pharmaceutical composition of any one of claims 1 to 7, wherein the gD, gH and gL encoded by the immunogen encoding region have the amino acid sequence of SEQ ID NOs 10, 6 and 7, respectively, and the gB encoded by the immunogen encoding region has the amino acid sequence of SEQ ID NOs 8 or 9; such as wherein the gD, gH and gL immunogen encoding regions have the nucleotide sequences of SEQ ID NOs 5, 1 and 2, respectively, or SEQ ID NOs 18, 15 and 16, respectively; and the gB immunogen encoding region has the nucleotide sequence of SEQ ID NO 3, 4 or 17.

11. The pharmaceutical composition according to any one of the preceding claims, wherein the one or more nucleic acid molecules are capable of expressing the plurality of herpes virus polypeptides in the form of a herpes virus fusion complex upon introduction into the vertebrate cell, or wherein the herpes virus polypeptides encoded by the one or more nucleic acid molecules are limited to those forming the fusion complex, and optionally also are herpes virus immunomodulators.

12. The pharmaceutical composition of any one of the preceding claims, wherein the one or more nucleic acid molecules encode an immunomodulatory agent, optionally CCL5 or VIT, wherein the one or more nucleic acid molecules are capable of expressing the immunomodulatory agent when introduced into the vertebrate cell; and/or wherein the composition comprises an immunomodulatory agent, optionally CCL5 or VIT; and/or wherein the composition comprises an adjuvant; and/or wherein the one or more nucleic acid molecules are supercoiled DNA; and/or wherein the nucleic acid molecules are aggregated with an aggregating agent; and/or wherein the composition comprises bupivacaine.

13. The pharmaceutical composition of any one of the preceding claims, wherein the one or more nucleic acid molecules encode one or more infectious agent antigens, wherein the one or more nucleic acid molecules are capable of expressing the one or more infectious agent antigens upon introduction into the vertebrate cell; and/or wherein the pharmaceutical composition further comprises one or more infectious agent antigens.

14. A pharmaceutical composition comprising a plurality of herpes virus polypeptides associated with a lipid membrane, wherein the pharmaceutical composition is formed by expressing the plurality of herpes virus polypeptides in human cells in vitro from one or more nucleic acid molecules comprising a plurality of immunogen encoding regions that collectively encode the plurality of herpes virus polypeptides, wherein each of the plurality of immunogen encoding regions has at least 90% sequence identity to a native encoding region of a corresponding native full-length herpes virus polypeptide from the same herpes virus species, wherein the plurality of herpes virus polypeptides are:

(ii) gB, gH and gL of the respective associated human herpesviruses.

15. The pharmaceutical composition according to claim 14, wherein the one or more nucleic acid molecules are as defined in any one of claims 2 to 13.

16. The pharmaceutical composition of claim 14 or 15, wherein the pharmaceutical composition further comprises one or more infectious agent antigens.

17. The pharmaceutical composition according to any one of claims 14 to 16, wherein the plurality of herpes virus polypeptides associated with a lipid membrane are provided in the form of a membrane, a membrane vesicle or an entire cell.

18. A pharmaceutical composition for use in medicine,

wherein the pharmaceutical composition comprises one or more nucleic acid molecules comprising a plurality of immunogenic coding regions that collectively encode a plurality of herpes virus polypeptides, wherein the one or more nucleic acid molecules are capable of expressing the plurality of herpes virus polypeptides when introduced into a vertebrate cell, wherein each of the plurality of immunogenic coding regions has at least 90% sequence identity to a native coding region of a corresponding native full length herpes virus polypeptide from the same herpes virus species, wherein the plurality of herpes virus polypeptides are:

Wherein the pharmaceutical composition is sterile; optionally wherein the pharmaceutical composition is as defined in any one of claims 1 to 17.

19. The pharmaceutical composition for use according to claim 18, for use in a method of inducing an immune response to a herpes virus.

20. The pharmaceutical composition for use according to claim 18, for use in a method of preventing or treating a herpes virus infection,

optionally wherein preventing a herpes virus infection comprises providing protection from an acute disease and/or infection; providing protection from build-up of latent infection; providing protection from reactivation latency infection and/or viral transmission; and/or provide protection from latent viral recurrence and disease;

optionally wherein treating the herpes virus infection comprises providing protection from establishing a latent infection; providing protection from reactivation latency infection and/or viral transmission; and/or to provide protection from latent viral recurrence and disease.

21. The pharmaceutical composition according to any one of claims 13 or 16 for use in a method of inducing an immune response to the one or more infectious agent antigens.

22. The pharmaceutical composition according to any one of claims 13 or 16 for use in a method of preventing or treating an infection caused by an infectious agent comprising the one or more infectious agent antigens.

23. A method of preparing a pharmaceutical composition according to any one of claims 1 to 13, comprising formulating one or more nucleic acid molecules as defined in any one of claims 1 to 13 with one or more physiologically acceptable diluents or excipients into a sterile composition.

24. A method of preparing a pharmaceutical composition according to any one of claims 14 to 17, comprising introducing one or more nucleic acid molecules as defined in claim 14 or 15 into a human cell in vitro, thereby allowing the human cell to express the plurality of herpes virus polypeptides from the one or more nucleic acid molecules, thereby obtaining the plurality of herpes virus polypeptides associated with a lipid membrane.

25. The method of claim 24, further comprising collecting membrane vesicles or whole cells comprising the plurality of herpesvirus polypeptides associated with a lipid membrane, and optionally purifying the membrane vesicles or whole cells.

26. The method of any one of claims 23 to 25, comprising formulating the pharmaceutical composition with one or more infectious agent antigens, and/or immunomodulators, and/or adjuvants.

27. A pharmaceutical composition comprising one or more nucleic acid molecules comprising a plurality of immunogenic coding regions that collectively encode a plurality of herpes virus polypeptides, wherein the one or more nucleic acid molecules are capable of expressing the plurality of herpes virus polypeptides when introduced into a vertebrate cell, wherein each of the plurality of immunogenic coding regions has at least 90% sequence identity to a native coding region of a corresponding native full length herpes virus polypeptide from the same herpes virus species, wherein the plurality of herpes virus polypeptides are:

Wherein the pharmaceutical composition is sterile.

28. The pharmaceutical composition according to claim 27, wherein the components of the pharmaceutical composition are as defined in any one of claims 2 to 13.