KR20200005165A - Noble severe fever with thrombocytopenia syndrome viruses - Google Patents

Abstract

The present invention relates to a novel genotype severe fever thrombocytopenia syndrome virus and a use thereof as an immunogenic composition. The severe fever thrombocytopenia syndrome viruses of the present invention are novel viruses which are genetically different from existing genotype thrombocytopenia syndrome viruses. Therefore, due to the nature of a vaccine which exhibits limited protective ability with only a certain genotype virus, the novel viruses of the present invention can be usefully used as vaccines having excellent cross-immunogenicity against SFTSV.

Description

Novel Severe Fever WITH THROMBOCYTOPENIA SYNDROME VIRUSES

The present invention relates to a novel severe febrile thrombocytopenia syndrome virus and its use as an immunogenic composition.

Severe fever with thrombocytopenia syndrome (SFTS) is a serious disease with symptoms such as high fever, vomiting, diarrhea, thrombocytopenia, white blood cell reduction, and multiple organ failure (Yu). XJ et al., N. Engl. J. Med. 2011; 364: 1523-32; Ding F et al Clin Infect Dis 2013; 56: 1682-3).

The causative agent of SFTS is SFTSV (severe fever thrombocytopenia syndrome virus) (HB29 strain) and belongs to the Bunyaviridae. The Burnavirus family is a negative-strand RNA virus that contains three segments: Orthobunyavirus, Hantavirus, Nairovirus, Plebovirus, and Tospovirus. It consists of five genes, including Tospovirus. SFTSV belongs to the Phlebovirus genus, which includes Rift valley fever virus. SFTSV was first reported in China in 2011 (Yu XJ et al. Ibid) and is a new strain of virus that continues to develop not only in China but also in Korea and Japan. SFTSV is a ball-shaped virus with a diameter of 80-100 nm. The virus has three genes: the large (L) segment, the medium (M) segment, and the small (S) segment, which are single-stranded negative sense RNA segments.

SFTS virus is mediated by Haemaphysalis longicornis, which is known to be widespread in Korea (Chae JS et al. J Vet Sci 2008; 9: 285-93; Kim CM et al. Appl) Environ Microbiol 2006; 72: 5766-76). Seroconversion and viremia of the SFTS virus have been found in breeding animals such as goats, sheep, cattle, pigs and dogs, and these animals are also believed to act as intermediate mediators in areas where the SFTS virus has spread (Zhao L et al. Emerg Infect). Dis 2013; 18: 963-5; Niu G et al. Emerg Infect Dis 2013; 19: 756-63). SFTSV is detected in the patient's blood, and in particular, SFTSV levels are very high in the blood of severe patients, and human-human propagation is possible through the blood (Tang X, Wu W, Wang H, et al. J Infect Dis 2013; 207 : 736-739.).

Antiviral agents for SFTSV have not yet been developed, and SFTS treatment is based on preservation therapy for organ failure such as blood transfusion and renal replacement therapy. In China, ribavirin dosing has been introduced as a treatment guideline since 2012, but the latest treatment results showed no difference in mortality between the ribavirin-administered and non-administered groups. Therefore, there is a need for a vaccine against SFTSV, but the vaccine has not yet been developed.

It is an object of the present invention to provide a novel hyperthermic thrombocytopenia virus and an immunogenic composition using the same.

In order to achieve the above object, the present invention provides a novel hyperthermic thrombocytopenia virus.

The present invention also provides an immunogenic composition for the prophylaxis or treatment of hyperthermic thrombocytopenia.

In addition, the present invention provides antibodies to Severe Thrombocytopenia virus or antigens thereof.

The present invention also provides a diagnostic kit for Severe Thrombocytopenia Virus.

The present invention also provides a method for detecting a hyperthermic thrombocytopenia virus antibody.

The present invention also provides a method of producing antisera against the severe febrile thrombocytopenia virus.

In addition, the present invention provides a method for providing information regarding the diagnosis of severe febrile thrombocytopenia.

Since the mesophilic thrombocytopenia virus of the present invention is a novel virus that is systematically belonging to type A and F and genetically different from the conventional thrombocytopenia virus, the novel viruses of the present invention are excellent in cross-immunogenicity against SFTSV. It can be usefully used as.

1 is a diagram showing the L gene flow diagram of two novel SFTSVs of the present invention and SFTSVs isolated from China, Japan, and Korea.
Figure 2 is a diagram showing the M gene of two novel SFTSV of the present invention and SFTSV isolated in China, Japan, Korea.
FIG. 3 is a diagram illustrating a S (NP) gene system of two novel SFTSVs of the present invention and SFTSVs separated from China, Japan, and Korea.
Figure 4 is a diagram showing the S (NS) gene hierarchy of two novel SFTSV of the present invention and SFTSV isolated from China, Japan, and Korea.
5 is a diagram showing amino acid mutation sites in the L, M and S genes of two novel viruses belonging to the type A and F genotypes of the present invention:
concensus: a sequence based on all types of SFTSV; And
Red box: A variation in certain genotypes, unlike consensus.
Figure 6 is a diagram confirming the effect of the vaccine inactivated the virus of the new detailed genotype A (CB11) and F (CB10) isolated from the present invention through survival, weight change and body temperature change.

Hereinafter, exemplary embodiments of the present invention will be described in detail with reference to the accompanying drawings. However, the following embodiments are presented by way of illustration of the present invention, and if it is determined that the detailed description of the well-known technology or construction well known to those skilled in the art may unnecessarily obscure the subject matter of the present invention, the detailed description thereof may be omitted. However, the present invention is not limited thereto. The invention is susceptible to various modifications and applications within the scope of the following claims and the equivalent scope thereof.

Also, the terminology used herein is a term used to properly express a preferred embodiment of the present invention, which may vary depending on a user, an operator's intention, or customs in the field to which the present invention belongs. Therefore, the definitions of the terms should be made based on the contents throughout the specification. Throughout the specification, when a part is said to "include" a certain component, it means that it can further include other components, without excluding other components unless specifically stated otherwise.

In one aspect, the invention provides that the amino acid 1061 of the protein expressed in ORF (6255bp) of the L gene (SEQ ID NO: 9) is glutamate and the 18th of the protein expressed in ORF (3222bp) of the M gene (SEQ ID NO: 10). Amino acid glycine, 562th amino acid glycine, 960th amino acid serine, 988th amino acid arginine or 1053th amino acid leucine, the protein NS (294aa) (SEQ ID NO: 12) expressed in ORF (1674bp) of the S gene Severe fever thrombocytopenia syndrome virus (SFTSV), wherein the 145th amino acid is lysine or the 171th amino acid glutamate.

In one embodiment, the hyperthermic thrombocytopenia virus belongs to genotype A, and the serine, the 18th amino acid of the protein expressed in the ORF (3222bp) of the M gene of the standard virus, previously classified as genotype A, is substituted with glycine, Or 960 th amino acid threonine may be a virus substituted with serine.

In one embodiment, the severe thrombocytopenia virus is L gene comprising the nucleotide sequence of SEQ ID NO: 1, M gene comprising the nucleotide sequence of SEQ ID NO: 2, S (NP) gene comprising the nucleotide sequence of SEQ ID NO: 3 And an S (NS) gene comprising a nucleotide sequence of SEQ ID NO: 4.

In one aspect, the invention provides that amino acid 1061 of the protein expressed in ORF (6255bp) of the L gene (SEQ ID NO: 13) is aspartic acid, and 18 of the protein expressed in ORF (3222bp) of the M gene (SEQ ID NO: 14). The first amino acid is serine, the 562th amino acid is serine, the 960th amino acid is threonine, the 988th amino acid is lysine or the 1053th amino acid is methionine, and the protein NS (294aa) expressed in ORF (1674bp) of the S gene (SEQ ID NO: 16) Refers to a hyperthermic thrombocytopenia virus wherein the 145th amino acid of is arginine or the 171th amino acid is aspartic acid.

In one embodiment, the hyperthermic thrombocytopenia virus belongs to genotype F, and glutamate, amino acid No. 1061 of the protein expressed in the ORF (6255bp) of the L gene of a virus previously classified as genotype F, is substituted with aspartic acid, Glycine, the 562th amino acid of the protein expressed in the ORF (3222bp) of the M gene, is substituted with serine, or leucine, the 1053th amino acid, is substituted with methionine, or the protein NS (294aa) expressed in the ORF (1674bp) of the S gene. The 145th amino acid of may be a virus substituted with arginine or the 171th amino acid glutamate with an aspartic acid.

In one embodiment, the severe thrombocytopenia virus is L gene comprising the nucleotide sequence of SEQ ID NO: 5, M gene comprising the nucleotide sequence of SEQ ID NO: 6, S (NP) gene comprising the nucleotide sequence of SEQ ID NO: 7 And an S (NS) gene comprising the nucleotide sequence of SEQ ID NO: 8.

In an embodiment of the present invention, the genetic analysis and phylogenetic classification of the isolated severe febrile thrombocytopenia virus showed that they belonged to type A and F, respectively, and their gene / amino acid sequences were severely febrile of the existing genotype. It was found to be a different virus from thrombocytopenia virus.

As used herein, the term “substitution” refers to the replacement of one or more amino acids or nucleotides by different amino acids or nucleotides, respectively.

Severe thrombocytopenia virus of the present invention is a minus single-stranded RNA virus belonging to the genus Bunyaviridae, phlebovirus. A spherical virus with a diameter of 80 to 100 nm, which is a small tick with a small tick. The genome is large (L). Medium (M). It consists of small (S) segments and contains RNA dependent RNA polymerase (RdRp), glycoprotein precursor (M), glycoprotein N (Gn), glycoprotein C (Gc), nucleocapsid protein (NP) and non-structural protein (NSs). Encode six proteins. Negative or antisense strands (antisense to the sense or plus strands that encode a viral protein) are proteins or genes encoded as antisense, and after the sense or plus strand RNA generation for expression of the gene into the protein, translation is performed therefrom. Protein is produced.

In one aspect, the present invention relates to an immunogenic composition for the prevention or treatment of febrile thrombocytopenia, comprising a febrile thrombocytopenia virus or an antigen thereof as an active ingredient.

In one embodiment, the immunogenic composition of the present invention may comprise inactivated hyperthermic thrombocytopenia virus and a pharmaceutically acceptable carrier or adjuvant.

In one embodiment, the immunogenic composition may be a vaccine composition, the form of which is a subunit vaccine, a vector vaccine, a chimeric vaccine, produced using the genes of a live poison vaccine, a dead poison vaccine, an attenuated mesophilic thrombocytopenia virus, It can be selected from the group consisting of DNA and RNA vaccines.

In one embodiment, the immunogenic composition is L gene comprising the nucleotide sequence of SEQ ID NO: 1, M gene comprising the nucleotide sequence of SEQ ID NO: 2, S (NP) gene and sequence comprising the nucleotide sequence of SEQ ID NO: 3 Severe thrombocytopenia virus comprising an S (NS) gene comprising the nucleotide sequence of No. 4; And an L gene comprising a nucleotide sequence of SEQ ID NO: 5, an M gene comprising a nucleotide sequence of SEQ ID NO: 6, an S (NP) gene comprising a nucleotide sequence of SEQ ID NO: 7, and an S including a nucleotide sequence of SEQ ID NO: 8 Severe thrombocytopenia viruses or their antigens, including the (NS) gene, may be included as an active ingredient.

For the preparation of immunogenic compositions (ie vaccines) of the invention, the virus or antigen thereof according to the invention is converted into a physiologically acceptable form. This can be done based on the experience of making vaccines used for vaccination against influenza (disclosed by Stickl, H. et al. [1974] Dtsch. Med. Wschr. 99, 2386-2392). For the preparation of vaccination, for example, viral particles are lyophilized in 100 ml of phosphate-buffered saline (PBS) in the presence of 1% human albumin and 2% peptone in ampoules, preferably in free ampoules. Alternatively, vaccination may be produced by sequential freeze-drying of the virus in the formulation. The formulation may be added to additives such as mannitol, dextran, sugar, glycine, lactose or polyvinylpyrrolidone or antioxidants or inert gases, stabilizers or recombinant proteins suitable for in vivo administration (e.g. human serum albumin) and Such as other adjuvants. The glass ampoule can then be sealed and stored for several months between 4 ° C. and room temperature. However, unless otherwise required, the ampoule may preferably be stored below −20 ° C.

For vaccination or treatment, the lyophilisate is dissolved in 0.1 to 0.5 ml of aqueous solution, preferably physiological saline or Tris buffer and systemically or topically, i.e. parenteral, subcutaneous, intramuscular or any known to those skilled in the art. It can be administered by other routes of administration. Dosage form, dosage and frequency of administration can be optimized by one skilled in the art in a known manner. Most commonly, however, patients receive a second vaccination about one to six weeks after the first vaccination.

In the present invention, the term "prevention" means any action which inhibits or delays the development, spread and recurrence of hyperthermic thrombocytopenia by administration of an immunogenic composition according to the present invention.

As used herein, the term "treatment" means any action that ameliorates or advantageously alters the symptoms of severe febrile thrombocytopenia and the complications thereof by administration of an immunogenic composition according to the present invention. Those skilled in the art to which the present invention pertains can refer to the data presented by the Korean Medical Association, etc., to know the exact criteria of the disease in which the composition of the present invention is effective, and to determine the extent of improvement, improvement and treatment. will be.

The term "therapeutically effective amount" used in combination with an active ingredient in the present invention means an amount effective for preventing or treating a disease caused by a transplant rejection, and the therapeutically effective amount of the composition of the present invention may be various factors, For example, it may vary depending on the administration method, the target site, the condition of the patient, and the like. Therefore, when used in humans, the dosage should be determined in an appropriate amount in consideration of both safety and efficiency. It is also possible to estimate the amount used in humans from an effective amount determined through animal testing. Such considerations when determining the effective amount include, for example, Hardman and Limbird, eds., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 10th ed. (2001), Pergamon Press; And E.W. Martin ed., Remington's Pharmaceutical Sciences, 18th ed. (1990), Mack Publishing Co.

The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. As used herein, the term "pharmaceutically effective amount" refers to an amount sufficient to treat the disease at a reasonable benefit / risk ratio applicable to medical treatment and not to cause side effects, and the effective dose level refers to Factors including health status, type of transplant, severity, drug activity, drug sensitivity, method of administration, time of administration, route of administration and rate of administration, duration of treatment, combination or concurrent use of drugs, and other well-known factors in the medical field It can be determined according to. The compositions of the present invention may be administered as individual therapeutic agents or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered in single or multiple doses. Taking all of the above factors into consideration, it is important to administer an amount that can achieve the maximum effect with a minimum amount without side effects, which can be readily determined by one skilled in the art.

The pharmaceutical compositions of the present invention may comprise carriers, diluents, excipients or combinations of two or more thereof conventionally used in biological preparations. As used herein, the term "pharmaceutically acceptable" means to exhibit a characteristic that is not toxic to cells or humans exposed to the composition. The carrier is not particularly limited so long as it is suitable for in vivo delivery of the composition, for example, Merck Index, 13th ed., Merck & Co. Inc. Compounds, saline solution, sterile water, Ringer's solution, buffered saline solution, dextrose solution, maltodextrin solution, glycerol, ethanol and one or more of these components can be mixed and used as needed. Conventional additives can be added. In addition, diluents, dispersants, surfactants, binders and lubricants may be additionally added to formulate into main dosage forms, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like. Furthermore, it may be preferably formulated according to each disease or component by a suitable method in the art or using a method disclosed in Remington's Pharmaceutical Science (Mack Publishing Company, Easton PA, 18th, 1990).

In one embodiment, the pharmaceutical composition may be one or more formulations selected from the group consisting of oral formulations, external preparations, suppositories, sterile injectable solutions and sprays, with oral or injectable formulations being more preferred.

As used herein, the term "administration" means providing a given substance to an individual or patient in any suitable manner, and according to the method desired, non-oral administration (eg, intravenous, subcutaneous, intraperitoneal). Or topically injectable formulations) or orally, and the dosage varies depending on the weight, age, sex, health condition, diet, time of administration, method of administration, rate of excretion and severity of the patient. Liquid preparations for oral administration of the composition of the present invention include suspensions, solvents, emulsions, syrups, and the like, and various excipients such as wetting agents, sweeteners, fragrances, and preservatives, in addition to water and liquid paraffin, which are commonly used simple diluents. And the like may be included together. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized formulations, suppositories, and the like. The pharmaceutical composition of the present invention may be administered by any device in which the active substance may migrate to the target cell. Preferred modes of administration and preparations are intravenous, subcutaneous, intradermal, intramuscular, drip and the like. Injections include non-aqueous solvents such as aqueous solvents such as physiological saline solution and ring gel solution, vegetable oils, higher fatty acid esters (e.g., oleic acid, etc.), and alcohols (e.g., ethanol, benzyl alcohol, propylene glycol, glycerin, etc.). Stabilizers (e.g. ascorbic acid, sodium bisulfite, sodium pyrosulfite, BHA, tocopherol, EDTA, etc.), emulsifiers, buffers for pH control, to prevent microbial growth Preservatives (eg, mercury nitrate, chimerosal, benzalkonium chloride, phenol, cresol, benzyl alcohol, etc.) may be included.

As used herein, the term "individual" means monkeys, cows, horses, sheep, pigs, chickens, turkeys, quails, cats, dogs, mice, mice, rabbits, or humans, including humans who may or may have the cancer. By any animal, including a guinea pig, "sample" can be whole blood, plasma, serum, urine or saliva isolated therefrom.

The pharmaceutical composition of the present invention may further comprise a pharmaceutically acceptable additive, wherein the pharmaceutically acceptable additives include starch, gelatinized starch, microcrystalline cellulose, lactose, povidone, colloidal silicon dioxide, calcium hydrogen phosphate , Lactose, mannitol, syrup, gum arabic, pregelatinized starch, corn starch, powdered cellulose, hydroxypropyl cellulose, opadry, sodium starch glycolate, carnauba lead, synthetic aluminum silicate, stearic acid, magnesium stearate, aluminum stearate, Calcium stearate, sucrose, dextrose, sorbitol, talc and the like can be used. The pharmaceutically acceptable additive according to the present invention is preferably included 0.1 parts by weight to 90 parts by weight based on the composition, but is not limited thereto.

In one aspect, the invention relates to an antibody produced in response to immunization with the virus of the invention or antigen thereof.

The antibodies are in the form of whole antibodies as well as functional fragments of antibody molecules. The whole antibody has a structure having two full length light chains and two full length heavy chains, each of which is linked by a heavy chain and a disulfide bond. The functional fragment of an antibody molecule means a fragment having an antigen binding function. Examples of the antibody fragment include (i) the variable region (VL) of the light chain and the variable region (VH) of the heavy chain, the constant region (CL) of the light chain, and Fab fragment consisting of the first constant region (CH1) of the heavy chain; (ii) a Fd fragment consisting of the VH and CH1 domains; (iii) a Fv fragment consisting of the VL and VH domains of a single antibody; (iv) a dAb fragment consisting of a VH domain (Ward ES et al., Nature 341: 544-546 (1989)); (v) an isolated CDR region; (vi) a bivalent fragment comprising two linked Fab fragments F (ab ') 2 fragments; (vii) single-chain Fv molecules (scFv) bound by peptide linkers that bind the VH and VL domains to form antigen binding sites; (viii) bispecific single-chain Fv dimers (PCT / US92 / 09965) and (ix) diabody WO94 / 13804, a multivalent or multispecific fragment produced by gene fusion.

In one aspect, the present invention relates to a diagnostic kit for Severe Thrombocytopenia virus comprising a Severe Thrombocytopenia virus or an antigen thereof, or an antibody thereto.

In one embodiment, the kit may comprise a virus sample comprising the virus according to the invention and a reagent for detecting the antigen-antibody complex. The antigen-antibody complex detection reagent includes a radioimmunoassay, ELISA (Enzyme linked immunosorbent assay) or immunofluorescence assay.

In one embodiment, antigen-antibody complex detection is performed by immunoelectrophoresis such as Ouchterlony plate, Western blot, Crossed IE, Rocket IE, Fused Rocket IE, Affinity IE, which can easily detect antibodies and / or antigens through antigen antibody binding. (Immuno Electrophoresis). Reagents or materials used in these methods are known and are for example antigen-antibody reactions, substrates that specifically bind antigens, nucleic acid or peptide aptamers, reactions with receptors or ligands or cofactors that interact with the complex. Can be detected or a mass spectrometer can be used. Reagents or materials that specifically interact with or bind to the antigen-antibody complexes of the present disclosure may be used in chip mode or with nanoparticles. The immunoassay or method of immunostaining is described in Enzyme Immunoassay, E. T. Maggio, ed., CRC Press, Boca Raton, Florida, 1980; Gaastra, W., Enzyme-linked immunosorbent assay (ELISA), in Methods in Molecular Biology, Vol. 1, Walker, J.M. ed., Humana Press, NJ, 1984 and the like. By analyzing the final signal intensity by the above-described immunoassay process, that is, by performing a signal contrast with a normal sample, it is possible to diagnose the infection.

In one aspect, the present invention relates to a diagnostic composition comprising a hyperthermic thrombocytopenia virus or antigen thereof, or an antibody thereto.

The compounds of the invention used in the diagnostic composition are preferably detectably labeled. Various methods available for labeling biomolecules are well known to those skilled in the art and are contemplated within the scope of the present invention. The methods are described in Tijssen, 'Practice and theory of enzyme immuno assays', Burden, RHand von Knippenburg (Eds), Volume 15 (1985), 'Basic methods in molecular biology'; Davis LG, Dibmer MD; Battey Elsevier (1990), Mayer et al., (Eds) 'Immunochemical methods in cell and molecular biology' Academic Press, London (1987), or in the series 'Methods in Enzymology', Academic Press, Inc.

There are many other markings and marking methods known to those skilled in the art. Examples of marker types that can be used in the present invention include enzymes, radioisotopes, colloidal metals, fluorescent compounds, chemiluminescent compounds and bioluminescent compounds.

Commonly used markers include fluorescents (eg, fluresin, rhodamine, Texas red, etc.), enzymes (eg, horseradish peroxidase, β-galactosidase, alkaline phosphatase), radioisotopes (eg, ³² P or ¹²⁵ I), biotin, digoxigenin, colloidal metal, chemiluminescent or bioluminescent compounds (eg dioxetane, luminol or acridinium). Labeling methods such as covalent binding of enzymes or biotinyl groups, iodide methods, phosphorylation methods, biotinylation methods and the like are well known in the art.

Detection methods include, but are not limited to, autoradiography, fluorescence microscopy, direct and indirect enzyme reactions, and the like. Commonly used detection assays include radioisotopes or non-radioisotope methods. These include Western blotting, overlay-analysis, Radioimmuno Assay (RIA) and Immune Radioimmunometric Assay (IRMA), Enzyme Immuno Assay (EIA), Enzyme Linked Immuno Sorbent Assay (ELISA), Fluorescent Immuno Assay (CIA) and Chemiluminoluminescent Immune Assay).

In one aspect, the present invention comprises the steps of contacting a sample isolated from a sample with a virus of the invention or an antigen thereof under conditions in which an antigen / antibody complex can be formed; And detecting an antagonistic thrombocytopenia virus antibody comprising detecting antigen / antibody complex formation.

In one aspect, the present invention comprises the steps of administering a virus or antigen of the present invention to a non-human animal in an amount effective to induce an immune response; And collecting antisera or plasma containing an antibody against the hyperthyroidism thrombocytopenia virus, the method comprising producing antisera against the hyperthyroidism thrombocytopenia virus in a non-human animal.

In one aspect, the present invention comprises the steps of contacting a sample isolated from a sample with a virus of the invention or an antigen thereof to form an antigen-antibody complex; And it relates to a method for providing information regarding the diagnosis of hyperthermic thrombocytopenia comprising detecting the formation of the complex.

The present invention will be described in more detail with reference to the following examples. However, the following examples are only intended to embody the contents of the present invention, and the present invention is not limited thereto.

Example 1. Virus Isolation

Severe fever thrombocytopenia syndrome virus, SFTSV, by real time PCR, PCR and ELISA analysis using blood, animal (goat and organic dog) blood, and wild mite homogenates of patients with suspected severe thrombocytopenia. Mesophilic thrombocytopenia virus) was confirmed. Specifically, the day before virus infection, VeroE6 cells were dispensed into 12-well plates, cultured to 60% cell density, cells were washed with PBS, and 300 μl of serum of suspected infected patients (whole blood at 3000 rpm). Serum obtained by centrifugation for a minute) was treated by treatment for 1 hour. After infection, serum was removed, cells were washed with PBS, exchanged with 1% FBS DMEM medium and incubated for 2 weeks. Two weeks later, RT-PCR (confirmed by reverse time real-time PCR) and immunofluorescence assay (immuno fluoresence assay) (mouse SFTSV NP antibody produced in the laboratory were the primary antibody and FITC counjugated antibody as the secondary antibody. Virus), and if the virus was not isolated, the virus was isolated by infecting the first supernatant with another VeroE6 cell. The isolated viruses were named CB11 / 2017 and CB10 / 2017.

Example 2. Genetic Analysis of Isolated Viruses

Viral CB11 / 2017 and CB10 / 2017 isolated using Vero E6 cells were subjected to reverse-transcription, PCR and NGS (Next generation sequencing), respectively, to obtain the respective L, M, S (NP, NS) gene full-length sequences. Confirmed. Specifically, cDNA was prepared by reverse-transcription PCR by extracting RNA from each virus. Thereafter, the genes of L, M, and S of each SFTS virus were subjected to PCR to obtain respective full-length genes. NGS method was used for gene sequencing, and the L, M, and S genes of each virus were subjected to tagmentation and index PCR using illumina nextera XT kit according to the protocol provided by illumina. After the final sample was produced using a illimina miniseq equipment Fasta Q file, the gene sequence of the generated file was analyzed by using the CLC main workbench program for the full-length gene sequence. As a result of genetic analysis by integrating the identified gene sequence with the genes of conventional viruses isolated from Korea, China and Japan, SFTSVs CB11 and CB10 isolated from the present invention are currently isolated from China or Korea (YuXJ et al. , N. Engl. J. Med. 2011) and a new genotype of SFTSV genetically different from the genes of Gangwon / 2012 virus first isolated in Korea. In addition, using the MEGA 7.0 program, the virus of the present invention and viruses isolated from Korea, China, and Japan were subjected to systematic gene analysis of the L, M, S (NP, NS) gene, the virus of the present invention Were identified as viruses belonging to the A and F groups. (FIGS. 1-4). Thus, two genotypes SFTSVs separated from the present invention are named as CB11 / 2017 and CB10 / 2017.

Example 3 Virus-Specific L, M, and S Genes Identify amino acid sequence differences

3-1. L gene amino acid sequence differences

As a result of analyzing the amino acid sequences of the L, M and S genes of the new detailed genotypes A and F viruses CB11 and CB10 isolated from the present invention, differences in the L, M and S genes were shown. Specifically, ORF (6255bp) of the L gene of the A / F genotype encodes RdRp, CB11 virus belonging to genotype A of the present invention, amino acid No. 1061 of RdRp appeared as glutamate (SEQ ID NO: 9), genotype F CB10 virus belonging to amino acid 1061 of RdRp appeared aspartic acid (SEQ ID NO: 13) (Fig. 5A and Table 1).

3-2. M gene amino acid sequence differences

As a result of analyzing the amino acid sequences of the L, M and S genes of the new detailed genotypes A and F viruses CB11 and CB10 isolated from the present invention, ORF of the M gene of the A / F genotype (3222bp) was used for the Gn and Gc proteins. The CB11 virus belonging to genotype A of the present invention showed that the 18th amino acid of the M gene ORF was glycine, the 562th amino acid glycine, the 960th amino acid serine, the 988th amino acid arginine, or the 1053th amino acid leucine. (SEQ ID NO: 10), the CB10 virus belonging to genotype F showed the 18th amino acid serine of the M gene ORF, the 562th amino acid serine, the 960th threonine, the 988th amino acid lysine, or the 1053th amino acid methionine (SEQ ID NO: 10). Number 14) (FIG. 5B and Table 1).

3-3. S gene amino acid sequence differences

As a result of analyzing the amino acid sequence of the L, M and S genes of the novel detailed genotypes A and F viruses CB11 and CB10 isolated from the present invention, ORF (1674bp) of the S gene in the A / F genotype was NS (882bp, 294aa). ) And the CB11 virus belonging to genotype A of the present invention, the 145th amino acid of the NS protein encoded by the S gene was shown as lysine or the 171th amino acid as glutamate (SEQ ID NO: 12). ), Genotype F virus showed arginine as the 145th amino acid of the NS protein encoded by the S gene or aspartic acid as the 171th amino acid (SEQ ID NO: 16) (FIG. 5C and Table 1).

Example 4 Gene Homology Comparison by Genotype

SFTSVs currently isolated in Korea were subjected to genetic analysis including the detailed genotypes A and F viruses CB11 and CB10 of the present invention, and analyzed the homology of the L, M and S genes for each genotype. As a result, there was about 96-100% nucleotide level between viruses belonging to the same genotype, while 93-100% relatively low gene homology between different genotype viruses (Tables 2 to 3). 5).

Homologous Comparison of L Genes

Comparison of homology of M genes

Homology Comparison of S (NP) Genes

Homology Comparison of S (NS) Genes

Example 5 Cross-Immunogenicity Analysis by Genotype

In order to analyze cross immunogenicity of each genotype, FRNT50 (fifty percent of Focus reduction neutralization test) was performed. Specifically, a large number of new detailed genotypes A and F viruses isolated from the present invention are multiplied, and then inactivated by addition of formalin (0.05%), respectively, and three or more virus isolations are used to determine whether they are incompatible. Confirmed. The inactivated whole vaccine was used to produce proteins through ultracentrifugation using 20% sucrose and then immunized to ferrets. Two weeks later, additional immunization was performed on the ferrets (two immunizations two weeks apart) and blood was drawn to separate serum. The separated serum was inactivated at 56 ° C. for 30 minutes, diluted to 1/10, and then diluted twice in fold. Virus diluted at 200 FFU / ml was reacted 1: 1 with 37 ° C. with virus diluted stepwise. VeroE6 cells dispensed in 6-well plates were washed and then infected with the reacted virus, washed after 1 hour, and then 0.8% DMEM agarose gel containing 1% FBS was poured onto the cells. After 5 days of infection, formalin was fixed and 3 hours later, three washes were performed, and 10% triton x-100 was treated at room temperature for 5 minutes. Then washed three times and performed blocking with 5% BSA. After incubation using the produced polyclonal NP antibody as a primary antibody, washed three times, and the reaction was washed by reacting the HRP conjugated antibody with a secondary antibody for 1 hour, and then developed by DAB to confirm the results (Table 6). Up to a 50% reduction in foucus formation in wells infected with viruses was interpreted as valid.

serum virus A F A 640 320 F 160 1280

In summary, SFTSV has various genotypes of viruses with various genes, and shows relatively high gene homology and high cross-immune response among viruses belonging to the same genotype, but relatively low gene homology with other genotype viruses. And low cross-immunogenicity, in order to show cross-immunogenicity against various genotypes, it can be inferred that only certain types of viruses show limited defense ability.

5-2. Check the vaccine effect

After a large amount of new detailed genotypes A and F viruses isolated from the present invention, the inactivation was performed by adding formalin (0.05%), respectively, and inactivation was confirmed through three virus isolations. The inactivated whole vaccines were immunized at 5 ferrets for each virus twice at two week intervals and then challenged at 1 × 10 ^7.6 / ml for each virus.

As a result of challenge vaccination, control animals died of all challenge virus infections within 10 days, but all ferrets of the vaccinated group survived, and body temperature and weight loss were confirmed after 2-8 days of infection, but later recovered. Could (Figure 6).

In summary, SFTSV has various genotypes of viruses with various genes, and shows relatively high gene homology and high cross-immune response among viruses belonging to the same genotype but relatively low gene homology with other genotype viruses. And low cross-immunogenicity, in order to show cross-immunogenicity against various genotypes, it can be inferred that only certain types of viruses show limited defense ability.

Therefore, it is considered that the novel viruses CB11 and CB10 of the present invention belonging to the detailed genotypes A and F of the present invention can be usefully used as vaccines having excellent cross-immunogenicity against SFTSV.

<110> I.D. Bio. <120> NOBLE SEVERE FEVER WITH THROMBOCYTOPENIA SYNDROME VIRUSES <130> PN1708-279 <160> 16 <170> KoPatentIn 3.0 <210> 1 <211> 6255 <212> DNA <213> Unknown <220> <223> severe fever thrombocytopenia syndrome virus A type L gene <400> 1 atggacttgg aagtgctttg tggtaggata aacgtggaga atgggctgtc tcttggagaa 60 ccaggcctgt acgaccaaat ctacgacagg cctgggctac cagacctaga tgtgactgtc 120 gatgccacag gtgtaacagt ggacatagga gctgtgccag actcagcatc acaactgggt 180 tcatcaatca atgctgggtt gatcacaatc cagctctctg aagcatataa gatcaatcat 240 gacttcacgt tctctggcct gtcaaagaca acagatcgac gcctctcaga ggtgttcccc 300 attacccatg atggttctga tgggatgacc cctgatgtga ttcacaccag attggatggg 360 accattgtgg tggttgaatt ttcaaccact aggagccata acattggggg cctggaggca 420 gcatatagga caaagataga aaaatatagg gacccaatct caaggcgtgt tgatatcatg 480 gagaacccga gggtcttctt tggcgctatt gtagtctcgt caggaggggt tctgtccaac 540 atgcccctga ctcaggatga ggcagaggag ctcatgtaca ggttttgcat tgccaatgag 600 atctacacca aggctagatc tatggatgca gacattgagc tacagaagag tgaggaagag 660 cttgaggcta ttagcagggc actatcattc ttcagtttgt ttgagcctaa cattgaaaga 720 gtagaaggaa cattccctaa ttcagaaatc gaaatgctgg aacagtttct ctcaactcca 780 gctgatgttg acttcatcac caagaccctc aaagcaaaag aggtagaggc ctatgctgat 840 ctttgtgaca gccactacct aaagcctgaa aaaaccattc aggagcgact agagatcaat 900 agatgtgagg ctattgacaa aactcaggac ctcctagctg gtctacatgc aaggagcaac 960 aagcaaacat cattgaatcg agggacagtc aaactcccgc cctggctacc aaagccgtca 1020 agtgagtcaa tagacatcaa gaccgactca ggctttggtt ccttaatgga tcatggcgca 1080 tatggtgagc tgtgggcaaa gtgccttcta gatgtctcgc tgggcaatgt ggagggggta 1140 gtcagcgacc ctgcaaaaga acttgacatt gccatctctg atgatcctga aaaagatacc 1200 cccaaagagg caaagataac ctataggcga ttcaaacctg ccttaagttc aagtgcccgt 1260 caagaatttt ctctccaagg agtggagggg aagaagtgga agagaatggc agcaaaccag 1320 aagaaagaga aggagtccca tgaggcattg agccctttct tggatgttga agacattggg 1380 gatttcctaa cattcaacaa tcttcttgca gattcgaggt atggagatga gtccgtccag 1440 agagcagtgt caatcttgtt ggaaaaggca tctgccatgc aagacacaga gctcactcat 1500 gccctcaacg attcattcaa gaggaaccta agcagtaatg tggttcagtg gtccctttgg 1560 gtctcttgtt tagcacagga gctagctagt gctctgaagc agcactgcag ggctggtgag 1620 ttcatcatca agaagctgaa attctggcct atctatgtca ttatcaagcc gaccaaatca 1680 tcatcccata tcttctacag cttagggatt cgcaaggctg acgtgacaag gaggctcact 1740 ggcagagtct tctctgatac cattgatgct ggggaatggg agctaacaga gttcaaaagc 1800 ctgaagacat gcaagcttac aaaccttgtc aacttgccat gcaccatgct gaactcaata 1860 gctttctgga gagagaagct gggcgtggct ccatggctgg ttcgaaaacc ttgttcagag 1920 ctcagggagc aggtgggcct gaccttcctg atcagtctgg aggacaagtc taagactgag 1980 gagatcatca ccttgacaag gtacacccag atggagggct ttgtctctcc ccccatgctg 2040 cctaagcccc aaaaaatgct agggaaactg gatggacctc tgagaactaa gctacaggtg 2100 tacctcctca ggaagcatct ggattgcatg gtgcgaattg cttctcagcc attcagccta 2160 atccctagag aggggagggt agaatggggg ggaacattcc atgccatctc aggccggtcc 2220 acaaaccttg agaatatggt gaacagctgg tacattgggt actacaagaa caaagaggag 2280 tcaacagagc taaatgccct tggagaaatg tataagaaga tcgtggagat ggaagaggac 2340 aagcccagca gccctgagtt tctagggtgg ggggacactg attcccctaa gaagcatgaa 2400 ttctcacgga gcttcctcag agctgcttgc tcatctctgg agagagaaat tgctcagcga 2460 catggaagac aatggaagca gaaccttgag gagcgtgtcc tgagagagat tgggaccaag 2520 aacattctgg accttgcatc catgaaggcc acaagcaact tttccaaaga ctgggagctc 2580 tactcagaag tccagaccaa agagtaccat aggtctaaac tgttggagaa gatggccaca 2640 ttgattgaga aaggggtcat gtggtacatt gatgctgtag gtcaggcatg gaaggcagtt 2700 ctagatgatg ggtgcatgcg aatctgtctc ttcaagaaga atcagcatgg tggcctcaga 2760 gagatctacg ttatggatgc gaatgcccga cttgtgcagt ttggggtcga gacaatggct 2820 aggtgtgtct gtgaactgag cccacatgag actgttgcca accctaggct caagaattcc 2880 atcatagaga accatgggct gaagtcagcc cgtagtcttg gccctggctc cataaacata 2940 aactcatcca atgacgccaa gaagtggaat caggggcact acacaacaaa gctagctcta 3000 gttctttgtt ggttcatgcc agccaaattc cacagattca tttgggctgc catttccatg 3060 tttcggagaa aaaagatgat ggtggaccta aggtttctag ctcacctcag ttctaaatct 3120 gagtctaggt catctgatcc gtttagggaa gcaatgacag atgccttcca tggtaatagg 3180 gaagtctcat ggatggacaa agggcgaact tacataaaga cagagacagg gatgatgcag 3240 ggcatactgc actttacatc cagtctccta cactcttgtg ttcagagctt ttacaagtct 3300 tatttcgtct cgaagctcaa agagggctac atgggggaaa gcatcagtgg ggtggtggac 3360 gtcatagaag gttctgacga ctctgcgatc atgatcagca tacgccctaa gtcagacatg 3420 gatgaagtcc gatcaaggtt ctttgttgct aacttgctcc actctgtcaa gttcttaaac 3480 cctttgtttg ggatttattc atcagagaaa tcaacagtga acacagtgta ttgtgtcgag 3540 tataactctg aattccattt ccacaggcac ttggttagac ccacactgag atggatagca 3600 gcgtctcacc aaatctcaga gactgaagcc cttgcaagca ggcaagagga ttactctaac 3660 cttctgaccc agtgcttgga agggggggcc tcattctctc ttacctacct catacagtgc 3720 gctcagctcc tacaccacta catgcttcta ggactatgct tacatccctt gtttggaacc 3780 ttcatgggga tgctgatatc agacccagat ccagccctag ggttctttct catggacaac 3840 cctgcattcg cagggggagc gggatttaga ttcaatctgt ggagagcctg caagacaaca 3900 gacctagggc ggaagtatgc atattatttc aatgagatac agggtaaaac aaagggagat 3960 gaggactaca gggctctgga cgccacatcg ggaggaactc tcagccactc tgttatggtg 4020 tactgggggg acaggaagaa gtatcaggcc ttattgagca ggatgggcct tcctgaagac 4080 tgggtggagc agatagatga gaatcctgga gtcctttaca ggagagcagc caacaagaag 4140 gaactactct taaagctggc agagaaggtt cattcacctg gtgtgactag cagcctgagt 4200 aaagggcatg tggtgcctcg ggtggtggca gcaggagtat acctcctctc acgccactgc 4260 tttcgcttta gctcaagcat ccatggcagg ggctcaacac agaaggctag ccttataaaa 4320 ctgttgatga tgtcttctat ttctgccatg aagcacgggg gctcactaaa ccctaatcag 4380 gagcgaatgc tcttccctca ggctcaggag tatgacaggg tgtgcacatt gcttgaggaa 4440 gttgaacacc taacagggaa atttgttgtt agggagagga acattgtcag gagccgcata 4500 gacctgttcc aagagccagt tgacttgcgg tgcaaggcag aagacctggt gtctgaggtg 4560 tggtttggcc tgaaaaggac taagcttggg ccccgtctcc tcaaggaaga gtgggacaaa 4620 cttagggcct catttgcatg gttgagcaca gacccatctg aaacattgag ggatggtcct 4680 tttcttagcc atgtgcagtt tagaaacttc atagcccacg ttgatgccaa atcaagatca 4740 gtcaggctcc taggtgcccc cgtgaagaaa tcaggcgggg tcaccactat aagccaagta 4800 gtcagaatga acttcttccc tggttttagc ctagaagctg agaagagctt agacaatcag 4860 gaaaggcttg agagcatctc catcctcaag catgtcttgt tcatggtctt gaatggccca 4920 tacactgagg agtacaagct ggaaatgatc atagaggcct tctctactct tgtgatacca 4980 cagccatcag aggtcatcag gaaatcaagg accatgactt tatgcctttt atcgaattac 5040 ttgtctagta ggggtgggtc cattctagac cagattgaga gggcacagtc aggcactcta 5100 ggaggattca gcaagcccca gaagacattc attaggccag gaggtggtgt tggctacaag 5160 ggaaaaggtg tgtggactgg agtgatggag gacacccatg tccaaattct gatagatgga 5220 gatgggacta gtaactggct tgaggagatc aggctcagta gtgatgccag gctttatgat 5280 gtcattgaat ccatccgaag gttatgtgat gaccttggga tcaacaacag ggtagcatct 5340 gcatatagag gtcattgcat ggttaggctg agtggattca agatcaagcc agcatcaagg 5400 actgacggct gtccagtcag gattatggaa aggggcttca ggattaggga actccaaaac 5460 ccagatgagg tcaagatgag agtgaggggc gacatcctta acctctctgt cactatacaa 5520 gaaggaaggg tcatgaacat cctaagctac aggccgagag acactgacat atcagagtca 5580 gccgcagcat acctctggag caatcgagac ctcttctcct ttgggaagaa ggagccatcc 5640 tgcagctgga tctgcttgaa aactcttgac aattgggcct ggtcacatgc ctcagttctc 5700 ctggcaaatg ataggaagac ccaaggcatt gacaatagag ctatggggaa catcttcagg 5760 gactgtctcg agggttctct aagaaagcaa gggctgatga ggtcaaaact cacagagatg 5820 gttgagaaga atgtagttcc tttaacaact caagagcttg tcgacatact ggaggaggac 5880 attgactttt cagatgtcat agctgtagag ctctcagagg gttcgcttga cattgaatcc 5940 atctttgatg gagcacctat cttgtggtct gctgaggtgg aagagtttgg agaaggagtg 6000 gtggctgtga gctattccag taagtactat catctaaccc tgatggacca agctgccatc 6060 acaatgtgtg caatcatggg caaggaagga tgtagagggc tccttactga gaagagatgc 6120 atggcagcca tacgagagca ggtacggcca ttcctcatat tcctacaaat tcctgaggac 6180 agcatttctt gggtatctga tcagttctgc gactccaggg gtcttgatga agagagcacc 6240 attatgtggg gttaa 6255 <210> 2 <211> 3222 <212> DNA <213> Unknown <220> <223> severe fever thrombocytopenia syndrome virus A type M gene <400> 2 atgatgaaag tcatctggtt ctcctctctg atctgcttag tcattcaatg cggtggggat 60 acaggcccaa tcatctgcgc aggacccatc cactcaaaca agagtgctga cataccccac 120 ctgcttggct actctgagaa gatttgtcag atagatcggc tgatacatgt ttcgtcatgg 180 cttagaaacc actcacaatt tcagggctac gtagggcagc gaggtggacg atctcaggtg 240 agctactacc cagctgaaaa ttcttactca aggtggagtg gacttctaag cccctgtgat 300 gctgattggc ttgggatgct tgtcgtgaag aaggccaagg ggtctgatat gatagttcca 360 gggccttcat acaaggggaa agtctttttt gaacggccaa cttttgatgg atacgtaggc 420 tggggctgtg gtagtgggaa gtctaggact gagtcaggtg agctctgcag ttcagactcc 480 gggactagtt ctggtcttct gccctcagat agggttctct ggataggtga tgttgcttgt 540 cagcctatga cacccatccc tgaggagaca tttctggagc tgaagagctt tagccaaagt 600 gaattcccag acatatgcaa aattgatggc attgtgttca accagtgtga gggtgagagt 660 ctacctcagc cctttgatgt tgcatggatg gatgttggcc actctcataa aatcatcatg 720 agggagcaca agaccaaatg ggtacaagag agctcatcca aggattttgt gtgctacaag 780 gaagggactg ggccttgttc tgaatcagaa gaaaagactt gcaagaccag tggatcatgc 840 aggggggaca tgcagttttg caaggtggca ggttgtgaac atggggaaga ggcatctgaa 900 gccaagtgca gatgctcact tgtgcacaag cccggggaag tcgttgtgtc atatggaggg 960 atgcgtgtca gaccaaagtg ctatggtttc tccagaatga tggcaacact ggaggtgaac 1020 gaaccagagc agaggaatgg tcaatgcact ggctgccatc tagaatgcat aaatgggggt 1080 gtgaggctaa tcactctaac cagtgagctc aagtcagcta ctgtctgcgc ttctcacttc 1140 tgcagttctg ccacaagtgg taagaaaagc acggagattc aattccactc aggatcattg 1200 gttgggaaaa cagcaatcca cgttaaaggg gcattggtag atggaactga attcacattt 1260 gagggtagtt gcatgttccc agatggttgt gatgcagtgg actgcacatt ctgtcgtgag 1320 tttctaaaaa atccccagtg ctaccctgca aagaagtggc tgttcatcat tattgtcatc 1380 ctccttggat atgcaggcct catgctactc accaatgttc ttaaggcaat tggggtttgg 1440 gggtcatggg tcatagctcc agtgaagcta gtgtttgcca tcataaagaa actaatgaga 1500 gctgtgagct gcctgatggg gaaattgatg gatagaggaa ggcaagtgat ccatgaggaa 1560 ataggggaga atagagaggg caaccaagat gatgttagga ttgagatggc cagacccagg 1620 agggtaaggc attggatgta ctcgcctgtc atcctgacta ttctagcaat ggggcttgct 1680 gagggctgtg atgagatggt ccatgctgat tctaaacttg tttcgtgcag gcaagggagc 1740 ggaaatatga aggaatgtgt cacaactggg agggcgcttc ttcctgcagt gaacccaggg 1800 caagaggcgt gtctgcactt cacggcacct ggaagtccgg actcaaaatg tctcaaaatt 1860 aaggttaaga ggatcaacct aaaatgtaaa aagtcatcat catattttgt tcctgatgcc 1920 cggtccaggt gtacatcagt gaggagatgt cgttgggcag gggactgcca gtctgggtgc 1980 ccccctcatt tcacatccaa ctccttttct gatgattggg caggtaagat ggacagggct 2040 ggtctaggat tcagtggctg ctctgatgga tgtggaggag cagcctgtgg ttgctttaat 2100 gcggcccctt cttgcatttt ctggaggaaa tgggtagaga atccacatgg gatcatctgg 2160 aaagtatctc catgtgccgc atgggtccca tcagcggtta tagagctaac aatgccctca 2220 ggggaggtga ggacattcca ccccatgagc ggaatcccca cacaagtctt caagggtgtg 2280 agtgtaactt acttgggctc agatatggag gtgtcaggct tgactgacct gtgtgagata 2340 gaagagctca agtcaaagaa gcttgcatta gctccctgca accaggctgg tatgggggtt 2400 gtaggcaagg ttggagagat acagtgcagt agcgaggaaa gtgcccgtac cataaaaaaa 2460 gatgggtgca tatggaatgc tgacctcgtg ggtatagagc tacgggtgga tgacgctgtg 2520 tgctactcta agatcactag tgtggaggca gttgcaaact actccgccat acccaccact 2580 attggggggc tgaggtttga gagaagccat gacagccagg gcaaaatatc tggtagcccc 2640 ctggacatca cagctataag aggatctttt tctatcaatt atagaggcct tcgactgagc 2700 ctctcagaaa ttactgctac ttgcacaggg gaagtgacaa atgtgagtgg gtgttattct 2760 tgcatgacag gcgccaaagt ctccatcaag ttgcatagca gcaaaaatag cactgcccat 2820 gtaagatgca aaggggatga gactgccttc agtgtcttgg agggagtcca tagctactct 2880 gtcagtctca gttttgatca tgcagtagtt gatgagcagt gccaactgaa ctgtggggga 2940 catgagagtc aagtgactct gagaggcaac ctcatcttcc tggatgtccc gaaatttgtg 3000 gatggcagct acatgcagac atatcatagc actgtgccca caggggcaaa tatcccaagc 3060 cctacagatt ggctaaatgc cttgtttggc aatgggctga gtaggtggat cctgggggtg 3120 ataggggtcc tactgggggg attggctctc tttttcttga tcatgtcttt gttcaagctg 3180 ggaacaaaac aggtatttcg atcgaggacg aagctggctt aa 3222 <210> 3 <211> 738 <212> DNA <213> Unknown <220> <223> severe fever thrombocytopenia syndrome virus A type NP gene <400> 3 atgtcagagt ggtccaggat tgcagtggag tttggtgagc agcagctcaa tttgactgag 60 cttgaggatt tcgcgagaga gctggcctat gaaggccttg atcctgcttt gatcatcaag 120 aagctgaagg agacaggtgg agatgattgg gtgaaggata cgaagttcat cattgtcttt 180 gccctgactc gaggcaataa gatcgtcaag gcatcaggga aaatgtctaa ctcagggtct 240 aagaggttga tggcactcca agagaaatat ggactggttg agagggcaga aaccaggctc 300 tcaatcactc ctgtgagggt agcgcagagc cttcccacct ggacatgtgc agcagcagca 360 gccttaaagg agtatctccc agtggggcca gccgtcatga acctgaaggt tgagaattat 420 ccacctgaga tgatgtgcat ggcctttggg tccctgattc caactgcagg agtatctgaa 480 gccacaacca agacccttat ggaggcctac tctctgtggc aagatgcctt caccaagact 540 atcaatgtga agatgcgtgg agccagcaag acagaagttt acaactcctt cagggaccct 600 ctccatgctg ctgtgaactc tgtcttcttt cccaatgatg ttcgggtgaa gtggctgaag 660 gccaagggaa tccttggccc agatggggtt cccagcagag ctgctgaggt tgctgctgct 720 gcttacagaa acctgtaa 738 <210> 4 <211> 882 <212> DNA <213> Unknown <220> <223> severe fever thrombocytopenia syndrome virus A type NS gene <400> 4 atgtcgctga gcaaatgctc caacgttgac ctcaaatctg tagcaatgaa tgctaacact 60 gttaggcttg agccttccct gggagagtac cccactctta ggagagacct cgtcgaatgc 120 tcttgtagtg tgttgacttt gtcaatggtc aagaggatgg gtaagatgac caacacagta 180 tggttgtttg gcaaccctaa aaatcctctt catcagcttg agcctggact tgagcagctg 240 ttagacatgt actacaagga catgaggtgc tactcccaga gagaactgag tgctcttagg 300 tggcctagtg ggaagccatc tgtatggttc ctacaggcag ctcatatgtt cttctccatc 360 aagaacagct gggcaatgga aaccggaaga gagaattggc ggggcctctt ccacaggata 420 acaaaaggcc aaaagtatct ttttgaaggg gacatgatat tggattctct tgaagccata 480 gagaagcgaa gacttagact tgggttgcct gagattctga taactggtct atccccaatt 540 ctggatgtgg ctctcctcca gatagagtca cttgcaaggc taagaggcat gagcttgaac 600 caccacttgt tcacttcttc ctcattgcgt aagcctctgt tagactgttg ggatttcttc 660 attcctatcc gcaaaaagaa gacagatggc tcatacagtg tcttggatga ggatgatgag 720 cctggggtcc tccagggtta cccatatctg atggcacact atttaaatag gtgcccattc 780 cacaacctca tcaggtttga tgaagaactg agaactgcag ccctgaacac catttgggga 840 agagattggc cagccattgg tgacctcccg aaggaggtct aa 882 <210> 5 <211> 6255 <212> DNA <213> Unknown <220> <223> severe fever thrombocytopenia syndrome virus F type L gene <400> 5 atggacttgg aagtgctttg tggtaggata aacgtggaga atgggctgtc tcttggagaa 60 ccaggcctgt acgaccaaat ctacgacagg ccagggctcc cagacctaga tgtgactgtc 120 gatgccacag gtgtgacagt ggacataggg gctgtgccag actcagcatc acaactgggt 180 tcatcaatca atgctgggtt gatcacaatc cagctctctg aagcatataa gatcaatcat 240 gacttcacgt tttctggtct gtcaaagaca acagaccgac gcctctcaga ggtattcccc 300 attacccatg atggttctga tgggatgacc cctgatgtga tccacaccag attggatgga 360 accatagtgg tggttgaatt ttcaaccact aggagccata acattggggg cctggaggca 420 gcatatagga caaagataga aaaatatagg gacccaatct caaggcgtgt tgatatcatg 480 gagaacccga gggtcttctt cggcgtaatt gtagtctcgt caggaggggt cctgtccaac 540 atgcccttga ctcaggatga ggcagaggag ctcatgtata ggttctgcat agccaatgag 600 atctacacta aggctagatc tatggatgca gacattgagc tacagaaaag tgaagaagag 660 cttgaggcta ttagcagggc actatcattc ttcagtttgt ttgagcctaa cattgaaaga 720 gtggaaggaa cattccctaa ttcagaaatc gagatgctgg agcagttcct ctcaacgcca 780 gctgatgttg acttcatcac caagaccctc aaagcaaaag aagtagaagc ctatgctgat 840 ctttgtgaca gccactacct aaagcctgag aaaaccatac aggagcggct agagatcaat 900 agatgtgagg ctattgacaa aactcaagac ctcctagctg gcctgcatgc aaggagcaac 960 aagcaaacat cattgaatcg agggacagtc aaactcccgc cctggctacc aaagccatca 1020 agtgagtcaa tagacatcaa gaccgactca ggctttggtt ccttaatgga tcatggcgca 1080 tatggtgagc tgtgggcaaa gtgccttcta gatgtctcgc taggcaatgt ggagggggta 1140 gtcagtgacc ctgcaaaaga acttgacatt gccatctctg atgatccaga aaaagacacc 1200 cccaaagagg caaagataac ctataggcga ttcaagcctg ccttaagttc gagtgcccgt 1260 caggaattct ctctccaagg agtggagggg aagaagtgga agagaatggc agcaaatcag 1320 aagaaagaga aggagtccca tgagacattg agcccgttct tggatgttga tgacatagga 1380 gatttcctaa cattcaacaa tcttcttgca gattcgaggt atggagacga gtccatccag 1440 agagctgtgt caatattgct ggaaaaggca tctgccatgc aagacacaga gctcactcat 1500 gccctcaacg attcatttaa gaggaatcta agcagcaatg tggttcagtg gtctctttgg 1560 gtctcctgtt tagcacagga gctagctagt gccctgaagc agcactgcag ggccggtgag 1620 ttcatcatca agaagctgaa gttctggcct atctatgtca ttatcaagcc gaccaaatca 1680 tcatcccata tcttctacag cttagggatc cgcaaggctg acgtgacaag gaggctaact 1740 ggtagagtct tctctgacac cattgatgct ggggaatggg aactaacaga gttcaaaagc 1800 ctgaagacat gcaagctcac gaatcttgtc aacttgccat gcaccatgct gaactcaata 1860 gctttctgga gagagaagct gggcgtggct ccatggctgg ttagaaagcc ctgttcagag 1920 ctcagggagc aggtgggcct gaccttcctg gtcagtctgg aggacaagtc taagactgag 1980 gagatcatca ccttgacaag gtacacccag atggagggct ttgtctctcc tcccatgctg 2040 cctaagcccc aaaagatgct agggaaactg gaagggcctt tgagaactaa gctacaggta 2100 tacctcctca ggaagcacct ggattgcatg gtgcgaattg cgtctcagcc tttcagccta 2160 atccctagag aggggagggt agagtgggga ggaacattcc atgccatctc aggccggtcc 2220 acaaaccttg agaacatggt gaacagctgg tacattgggt actacaagaa caaagaggag 2280 tcaacagagc taaatgccct cggagaaatg tataagaaga ttgtggagat ggaagaggac 2340 aagcccagca gtcctgagtt tctagggtgg ggggacacag attcccccaa gaagcatgaa 2400 ttctcacgga gcttcctcag agctgcttgc tcatctctag agagagaaat tgctcagcga 2460 catgggaggc aatggaagca gaaccttgag gagcgtgtcc tgagagagat tggggccaag 2520 aacatcctgg accttgcatc catgaaggct acaagcaact tttccaaaga ctgggagctc 2580 tactcagaag tccagaccaa agagtaccat aggtccaaac tactggagaa gatggccaca 2640 ttgattgaga agggggttat gtggtacatt gatgctgtgg gccaggcatg gaaggcagtt 2700 ctggatgacg ggtgcatgcg aatctgtctc ttcaaaaaga atcagcatgg tggccttaga 2760 gagatctacg ttatggatgc gaatgcccgg ctcgtgcagt ttggggttga gaccatggct 2820 aggtgtgtct gtgagctgag ccctcatgag actgttgcta accctcggct caagaattcc 2880 atcatagaga accatggact gaagtcagcc cgtagtcttg gccctggctc tataaacata 2940 aactcatcca atgatgccaa gaagtggaat caggggcact acacaacaaa gctagcttta 3000 gttctttgtt ggttcatgcc agctaaattc cacagattca tttgggctgc catttccatg 3060 tttcggagaa aaaagatgat ggtggaccta aggtttttag ctcacctcag ttctaaatct 3120 gagtctaggt catctgatcc gtttagggaa gcaatgacag atgccttcca tggtaatagg 3180 gatgtctcat ggatggacaa agggcgaact tacattaaga cagagacagg aatgatgcag 3240 ggcatactgc acttcacatc cagtctcctc cactcttgtg ttcagagctt ctacaagtct 3300 tatttcgtct cgaagctcaa ggagggctac atgggggaaa gcatcagtgg ggtggtggat 3360 gtcatagaag gctctgacga ctcagcgatc atgattagca tacgccctaa gtcagacatg 3420 gatgaagttc gatccaggtt ctttgttgct aacttgctcc actctgttaa gttcttgaat 3480 ccattgtttg ggatttattc atcagagaaa tcaacagtga acacagtgta ttgtgtcgaa 3540 tataactctg aattccattt ccacaggcac ttggttagac ccacactgag atggatagca 3600 gcgtctcatc aaatctcaga gactgaagcc cttgcaagca ggcaagagga ttactccaac 3660 cttctaaccc agtgcttgga aggaggggcc tcattctctc ttacctacct catacagtgc 3720 gctcagctcc tgcaccacta catgcttcta ggactttgct tacatcccct gtttggaacc 3780 ttcatgggga tgctgatatc agacccagat ccagccctag ggttcttcct catggacaac 3840 cctgcattcg cagggggagc aggatttaga ttcaatctgt ggagagcctg caagactaca 3900 gaccttgggc ggaagtatgc atattatttt aatgagatac agggtaagac aaagggagat 3960 gaggactaca gagctctgga cgccacatcg ggaggaactc tcagccactc tgttatggtg 4020 tactgggggg acaggaagaa gtatcaagcc ttattgaaca ggatgggcct tcctgaagac 4080 tgggtggagc agatagatga gaatcctgga gtcctctaca ggagagctgc caacaagaaa 4140 gaactgctct taaagctggc agagaaggtt cattcacctg gtgtgactag cagcctgagt 4200 aaagggcatg tagtgcctcg ggtggtggca gcaggagtgt acctcctctc acgtcattgc 4260 tttcgcttta gttcaagcat ccatggcagg ggctcaacgc agaaggctag ccttataaaa 4320 ttgctgatga tgtcttctat ttctgccatg aagcatgggg gctcactgaa ccctaaccag 4380 gagcgaatgc tcttccctca ggctcaagag tatgacagag tatgcacatt gcttgaggaa 4440 gttgaacacc taacagggaa atttgttgtt agggagagaa acattgtcag gagccgcata 4500 gatttgttcc aagagccagt ggacttgcgg tgcaaggcag aagatctggt gtcagaggtg 4560 tggtttggcc tgaaaaggac taaacttgga ccccgtctcc tcaaggaaga gtgggataaa 4620 cttagggcct catttgcatg gctgagcaca gacccatctg aaacattgag ggatggtcct 4680 tttcttagcc atgtgcagtt taggaacttc atagcccacg ttgatgccaa atcaagatca 4740 gtcaggctcc taggtgcccc cgtgaagaag tcaggtgggg tcaccaccat aagccaagtg 4800 gtcagaatga acttcttccc tggttttagc ctagaagctg agaagagctt agacaatcag 4860 gaaagacttg agagtatctc catcctcaag catgtcttgt tcatggtctt gaatggccca 4920 tacactgagg agtacaagct ggagatgatc atagaggcct tctctactct tgtgatacca 4980 cagccatcag aggtcatcag gaaatcaagg accatgactt tatgcctctt atcgaattac 5040 ttgtccagta ggggtgggtc cattctagac caaattgaga gggcacagtc aggcactcta 5100 ggaggcttca gcaagcccca gaagacattt attaggccag gaggtggtgt tggctacaag 5160 ggaaaaggtg tgtggactgg agtgatggag gacacccatg ttcaaattct gatagatgga 5220 gatggtacaa gtaactggct cgaggagatc aggctcagta gtgatgctag gctttatgat 5280 gtcattgaat ccatccgaag gttatgtgat gaccttggga tcaacaacag ggtggcatct 5340 gcatatagag gccattgtat ggttaggctg agtggattca agatcaagcc agcatcaagg 5400 actgacggct gtccagtcag gattatggaa aggggcttca gaattaggga acttcaaaac 5460 ccagatgagg tcaaaatgag agtgaggggc gacatcctca acctctctgt cactatacaa 5520 gaaggaaggg tcatgaacat cctaagctac aggccgagag acactgatat atcagagtca 5580 gccgcagcat acctctggag caatcgagac ctcttctcct ttgggaagaa ggagccgtcc 5640 tgcagctgga tctgcttgaa aactctagat aattgggcct ggtcacatgc ctcagttctc 5700 ctggcaaatg ataggaagac ccaaggtatt gacaatagag ctatggggaa cattttcagg 5760 gactgtctcg agggttctct tagaaagcaa gggttgatga ggtcaaagct cacagagatg 5820 gtggagaaga atgtagttcc tttaacaact caagagcttg tcgacatcct ggaggaggac 5880 attgactttt cagatgtcat agctgtagag ctctcagagg gatcacttga cattgaatcc 5940 atctttgatg gggcacctat cttgtggtct gctgaggtgg aagagtttgg agaaggagtg 6000 gtggctgtga gctattcaag caagtactat catctgaccc tgatggacca agctgccatc 6060 acaatgtgtg caatcatggg taaggaaggc tgcagagggc tccttactga gaagagatgc 6120 atggcagcca tacgagagca ggtgcggcca ttcctcatat tcctgcaaat tcctgaggac 6180 agcatttctt gggtgtctga tcagttctgc gactccaggg gtcttgatga agagagcacc 6240 attatgtggg gttaa 6255 <210> 6 <211> 3222 <212> DNA <213> Unknown <220> <223> severe fever thrombocytopenia syndrome virus F type M gene <400> 6 atgatgaaag tcatctggtt ctcctctctg atctgctttg tcattcaatg cagtggggac 60 tcaggcccaa tcatctgcgc aggacccatc cactcaaaca agagtgctga catacctcac 120 ctgctgggtt actctgagaa gatatgtcag atagatcggc tgatacatgt ttcgtcatgg 180 ctcaggaacc actcacaatt tcagggctac gtaggccagc gaggtggacg ctctcaggtg 240 agctactacc cagctgaaaa ttcttactca aggtggagtg ggcttctaag cccctgtgat 300 gctgattggc ttgggatgct tgtcgtgaag aaggccaagg ggtctgatat gatagttcct 360 gggccttcat acaagggaaa agtctttttt gagcggccaa cttttgatgg atatgtaggc 420 tggggctgtg gcagtgggaa gtctaggaca gagtcaggag agctctgcag ttcagactcg 480 gggactagct ctggtcttct gccctcagat agggttctct ggataggtga tgttgcttgt 540 cagcctatga cacccatccc tgaagagaca tttctggagc tgaagagttt tagccaaagt 600 gaattcccag acatatgcaa aattgatggc attgtattca accagtgtga gggtgagagc 660 ctacctcagc cctttgatgt tgcatggatg gatgttggcc actctcataa aatcatcatg 720 agggagcaca agaccaaatg ggtgcaagag agctcatcca aggattttgt gtgctacaag 780 gaagggactg ggccttgttc tgaatcagaa gaaaagactt gcaagaccag tggatcatgc 840 aggggggaca tgcagttctg caaggtagca ggttgtgaac atggggaaga ggcatctgaa 900 gccaagtgta gatgctcact tgtgcacaag cccggagaag tcgttgtgtc atatggaggg 960 atgcgtgtca gaccaaagtg ctatggtttc tccagaatga tggcaacact ggaggtgaac 1020 caaccagagc aaaggattgg tcaatgcact ggctgccatc tggaatgcat aaatgggggt 1080 gtgaggctaa taactctaac cagtgagctc aagtcagcta ctgtctgtgc ttctcacttt 1140 tgtagttctg ccacaagtgg caagaaaagc acggagattc aattccactc aggatcattg 1200 gttgggaaaa cagcaataca cgtcaaaggg gcattggtag atggaactga attcacattt 1260 gagggtagtt gcatgttccc agatggttgt gatgcggtgg actgcacttt ctgtcgtgag 1320 tttctaaaaa atccccagtg ctaccctgca aagaagtggc tgttcatcat tattgtcatc 1380 ctccttgggt atgcaggcct catgctactc accaatgtcc tcaaggcaat tgggatttgg 1440 ggatcatggg tcatagctcc agtgaagcta atatttgcca tcataaagaa actaatgaga 1500 actgtgagct gcttgatggg gaaattgatg gataggggaa ggcaagtgat ccatgaggag 1560 ataggggaga atagagaggg caaccaagat gatgttagga ttgagatggc aagacccaga 1620 agggtaaggc attggatgta ctcacctgtc atcctgacta ttttagcaat agggcttgct 1680 gagagctgtg atgagatggt ccatgctgat tctaagcttg tttcatgcag gcaagggagc 1740 ggaaatatga aggaatgtgt cacaactggg agggcgcttc ttcctgcggt gaacccaggt 1800 caagaggcat gtctgcactt cacggcacct gggagtccgg actcaaaatg tctcaaaatt 1860 aaggttaaga ggatcaacct aaaatgtaag aagtcatcat catattttgt tcctgatgcc 1920 cggtccagat gtacatcagt gaggagatgt cgttgggctg gagactgcca gtctgggtgc 1980 ccccctcatt tcacatccaa ctccttttct gatgattggg caggtaagat ggacagggct 2040 ggtctagggt tcagtggctg ctctgatgga tgtggaggag cagcctgcgg ctgctttaat 2100 gcagcccctt cttgcatctt ctggaggaaa tgggtagaga acccacatgg gatcatctgg 2160 aaagtgtctc cttgtgccgc atgggtccca tcggcagtca tagagctaac aatgccctca 2220 ggggaggtga ggacattcca ccccatgagt ggcatcccca cacaagtctt caagggtgtg 2280 agtgtgactt acttgggctc agatatggag gtgtctggct tgactgacct atgtgagata 2340 gaggagctca agtccaagaa gctggcatta gctccctgca accaggctgg catgggggtt 2400 gtaggcaagg ttggagagat acagtgcagt agcgaggaaa gtgcccgtac cataaaaaaa 2460 gatgggtgca tatggaatgc agaccttgtg ggcatagagc tacgagtgga tgacgctgtg 2520 tgctactcta agatcactag tgtggaagca gttgcaaact actctgccat acccaccact 2580 attggggggc tgaggtttga gagaagccat gacagccagg gtaaaatatc tggtagcccc 2640 ctggacatca cagctataag aggatctttt tctgttaatt atagaggcct tcgactgagc 2700 ctctcagaaa ttactgctac ctgcacaggg gaggtgacaa atgtgagtgg atgttattct 2760 tgcatgacag gcgccaaagt ctctatcaaa ctacatagca gcaaaaatag cactgcccat 2820 gtaagatgca aaggggatga gactgcattc agtgtcttgg agggggtcca tagttacact 2880 gtcaatctca gttttgacca tgcagtggtc gatgagcagt gccaactgaa ctgtggggga 2940 catgagagtc aagtgactct aaaaggcaac cttatcttcc tggatgtccc aaaatttgtg 3000 gatggcagct acatgcagac atatcatagc actgtgccca caggggcaaa tatcccaagc 3060 ccaacagact ggctgaatgc cttgtttggc aatgggctga gtaggtggat cctgggggtg 3120 ataggggttc tacttggggg gttggctctc tttttcatga ttatgtcttt gttcaagctg 3180 ggaacaaaac aggtatttcg atcaaggacg aagctggctt ag 3222 <210> 7 <211> 738 <212> DNA <213> Unknown <220> <223> severe fever thrombocytopenia syndrome virus F type NP gene <400> 7 atgtcagagt ggtccaggat tgcagtggag tttggtgagc agcagctcaa tttgactgag 60 cttgaggatt tcgcgagaga gctagcctat gaaggccttg atcctgcttt gatcatcaag 120 aagctgaagg agacaggtgg agatgactgg gtgaaggata ctaagttcat cattgtcttt 180 gccctgactc gaggcaataa gatcgtcaag gcatcaggga agatgtcaaa ctcagggtca 240 aagaggttga tggcactcca ggagaaatat gggctggttg agagggcaga gaccaggctc 300 tcaatcaccc ctgtaagggt agcgcagagc ctccccactt ggacatgtgc tgcagcagca 360 gccttaaagg agtatctccc agtggggcca gccgtcatga acctgaaggt tgagaattat 420 cccccagaga tgatgtgcat ggccttcggg tccctgattc caactgcagg ggtatctgaa 480 gccacgacca agaccctgat ggaggcttac tctttatggc aagatgcctt caccaagact 540 atcaatgtga agatgcgcgg agccagcaag acagaagttt acaactcctt cagggatcct 600 ctccatgctg ctgtgaactc tgtcttcttc cccaatgatg ttcgggtgaa gtggctgaag 660 gccaagggaa tccttggccc agatggggtc cccagcagag ctgctgaggt tgctgctgct 720 gcttacagga acctgtaa 738 <210> 8 <211> 882 <212> DNA <213> Unknown <220> <223> severe fever thrombocytopenia syndrome virus F type NS gene <400> 8 atgtcgctga gcaaatgctc caacgttgat ctcaaatctg ttgcaatgaa tgccaacaca 60 gtcaggcttg agccatctct aggagagtac cccactctta ggagggacct cgttgaatgc 120 tcttgcagtg tgttgactct gtcgatggtc aagaggatgg gtaagatgac caacacagta 180 tggttgtttg gcaaccccaa aaatcctctt caccagcttg agcctggact tgagcagcta 240 ttggacatgt actacaagga catgaggtgc tactcccaga gagagctgag tgctcttagg 300 tggcctagtg ggaagccatc tgtatggttc ttgcaggcag ctcatatgtt cttctccatc 360 aagaacagct gggcaatgga aactgggaga gagaactggc ggggcctctt ccacaggata 420 acaaaaggcc gaaggtatct ttttgaaggg gacatgatat tggattctct agaagccata 480 gagaagcgaa ggcttagact tgggttacct gatatcctaa taactggact gtccccaatt 540 ctggatgtgg ccctccttca gatagagtca cttgcaaggc taagaggcat gagcttgaac 600 caccacttgt tcacttcttc ctcattgcgt aagcctctgt tggactgttg ggacttcttt 660 atccctatcc gcaaaaagaa gacagatggc tcatacagtg tcttggatga ggatgatgag 720 cctggggtcc ttcaaggtta cccatatctg atggcacact atttaaacag gtgcccattc 780 cacaacctca tcaggtttga tgaggagctg agaactgcag ccctgaacac catctgggga 840 agagattggc cagccattgg tgaccccccg aaggaggtct aa 882 <210> 9 <211> 2085 <212> PRT <213> Unknown <220> <223> severe fever thrombocytopenia syndrome virus A type L <400> 9 Met Asp Leu Glu Val Leu Cys Gly Arg Ile Asn Val Glu Asn Gly Leu   1 5 10 15 Ser Leu Gly Glu Pro Gly Leu Tyr Asp Gln Ile Tyr Asp Arg Pro Gly              20 25 30 Leu Pro Asp Leu Asp Val Thr Val Asp Ala Thr Gly Val Thr Val Asp          35 40 45 Ile Gly Ala Val Pro Asp Ser Ala Ser Gln Leu Gly Ser Ser Ile Asn      50 55 60 Ala Gly Leu Ile Thr Ile Gln Leu Ser Glu Ala Tyr Lys Ile Asn His  65 70 75 80 Asp Phe Thr Phe Ser Gly Leu Ser Lys Thr Thr Asp Arg Arg Leu Ser                  85 90 95 Glu Val Phe Pro Ile Thr His Asp Gly Ser Asp Gly Met Thr Pro Asp             100 105 110 Val Ile His Thr Arg Leu Asp Gly Thr Ile Val Val Val Glu Phe Ser         115 120 125 Thr Thr Arg Ser His Asn Ile Gly Gly Leu Glu Ala Ala Tyr Arg Thr     130 135 140 Lys Ile Glu Lys Tyr Arg Asp Pro Ile Ser Arg Arg Val Asp Ile Met 145 150 155 160 Glu Asn Pro Arg Val Phe Phe Gly Ala Ile Val Val Ser Ser Gly Gly                 165 170 175 Val Leu Ser Asn Met Pro Leu Thr Gln Asp Glu Ala Glu Glu Leu Met             180 185 190 Tyr Arg Phe Cys Ile Ala Asn Glu Ile Tyr Thr Lys Ala Arg Ser Met         195 200 205 Asp Ala Asp Ile Glu Leu Gln Lys Ser Glu Glu Glu Leu Glu Ala Ile     210 215 220 Ser Arg Ala Leu Ser Phe Phe Ser Leu Phe Glu Pro Asn Ile Glu Arg 225 230 235 240 Val Glu Gly Thr Phe Pro Asn Ser Glu Ile Glu Met Leu Glu Gln Phe                 245 250 255 Leu Ser Thr Pro Ala Asp Val Asp Phe Ile Thr Lys Thr Leu Lys Ala             260 265 270 Lys Glu Val Glu Ala Tyr Ala Asp Leu Cys Asp Ser His Tyr Leu Lys         275 280 285 Pro Glu Lys Thr Ile Gln Glu Arg Leu Glu Ile Asn Arg Cys Glu Ala     290 295 300 Ile Asp Lys Thr Gln Asp Leu Leu Ala Gly Leu His Ala Arg Ser Asn 305 310 315 320 Lys Gln Thr Ser Leu Asn Arg Gly Thr Val Lys Leu Pro Pro Trp Leu                 325 330 335 Pro Lys Pro Ser Ser Glu Ser Ile Asp Ile Lys Thr Asp Ser Gly Phe             340 345 350 Gly Ser Leu Met Asp His Gly Ala Tyr Gly Glu Leu Trp Ala Lys Cys         355 360 365 Leu Leu Asp Val Ser Leu Gly Asn Val Glu Gly Val Val Ser Asp Pro     370 375 380 Ala Lys Glu Leu Asp Ile Ala Ile Ser Asp Asp Pro Glu Lys Asp Thr 385 390 395 400 Pro Lys Glu Ala Lys Ile Thr Tyr Arg Arg Phe Lys Pro Ala Leu Ser                 405 410 415 Ser Ser Ala Arg Gln Glu Phe Ser Leu Gln Gly Val Glu Gly Lys Lys             420 425 430 Trp Lys Arg Met Ala Ala Asn Gln Lys Lys Glu Lys Glu Ser His Glu         435 440 445 Ala Leu Ser Pro Phe Leu Asp Val Glu Asp Ile Gly Asp Phe Leu Thr     450 455 460 Phe Asn Asn Leu Leu Ala Asp Ser Arg Tyr Gly Asp Glu Ser Val Gln 465 470 475 480 Arg Ala Val Ser Ile Leu Leu Glu Lys Ala Ser Ala Met Gln Asp Thr                 485 490 495 Glu Leu Thr His Ala Leu Asn Asp Ser Phe Lys Arg Asn Leu Ser Ser             500 505 510 Asn Val Val Gln Trp Ser Leu Trp Val Ser Cys Leu Ala Gln Glu Leu         515 520 525 Ala Ser Ala Leu Lys Gln His Cys Arg Ala Gly Glu Phe Ile Ile Lys     530 535 540 Lys Leu Lys Phe Trp Pro Ile Tyr Val Ile Ile Lys Pro Thr Lys Ser 545 550 555 560 Ser Ser His Ile Phe Tyr Ser Leu Gly Ile Arg Lys Ala Asp Val Thr                 565 570 575 Arg Arg Leu Thr Gly Arg Val Phe Ser Asp Thr Ile Asp Ala Gly Glu             580 585 590 Trp Glu Leu Thr Glu Phe Lys Ser Leu Lys Thr Cys Lys Leu Thr Asn         595 600 605 Leu Val Asn Leu Pro Cys Thr Met Leu Asn Ser Ile Ala Phe Trp Arg     610 615 620 Glu Lys Leu Gly Val Ala Pro Trp Leu Val Arg Lys Pro Cys Ser Glu 625 630 635 640 Leu Arg Glu Gln Val Gly Leu Thr Phe Leu Ile Ser Leu Glu Asp Lys                 645 650 655 Ser Lys Thr Glu Glu Ile Ile Thr Leu Thr Arg Tyr Thr Gln Met Glu             660 665 670 Gly Phe Val Ser Pro Pro Met Leu Pro Lys Pro Gln Lys Met Leu Gly         675 680 685 Lys Leu Asp Gly Pro Leu Arg Thr Lys Leu Gln Val Tyr Leu Leu Arg     690 695 700 Lys His Leu Asp Cys Met Val Arg Ile Ala Ser Gln Pro Phe Ser Leu 705 710 715 720 Ile Pro Arg Glu Gly Arg Val Glu Trp Gly Gly Thr Phe His Ala Ile                 725 730 735 Ser Gly Arg Ser Thr Asn Leu Glu Asn Met Val Asn Ser Trp Tyr Ile             740 745 750 Gly Tyr Tyr Lys Asn Lys Glu Glu Ser Thr Glu Leu Asn Ala Leu Gly         755 760 765 Glu Met Tyr Lys Lys Ile Val Glu Met Glu Glu Asp Lys Pro Ser Ser     770 775 780 Pro Glu Phe Leu Gly Trp Gly Asp Thr Asp Ser Pro Lys Lys His Glu 785 790 795 800 Phe Ser Arg Ser Phe Leu Arg Ala Ala Cys Ser Ser Leu Glu Arg Glu                 805 810 815 Ile Ala Gln Arg His Gly Arg Gln Trp Lys Gln Asn Leu Glu Glu Arg             820 825 830 Val Leu Arg Glu Ile Gly Thr Lys Asn Ile Leu Asp Leu Ala Ser Met         835 840 845 Lys Ala Thr Ser Asn Phe Ser Lys Asp Trp Glu Leu Tyr Ser Glu Val     850 855 860 Gln Thr Lys Glu Tyr His Arg Ser Lys Leu Leu Glu Lys Met Ala Thr 865 870 875 880 Leu Ile Glu Lys Gly Val Met Trp Tyr Ile Asp Ala Val Gly Gln Ala                 885 890 895 Trp Lys Ala Val Leu Asp Asp Gly Cys Met Arg Ile Cys Leu Phe Lys             900 905 910 Lys Asn Gln His Gly Gly Leu Arg Glu Ile Tyr Val Met Asp Ala Asn         915 920 925 Ala Arg Leu Val Gln Phe Gly Val Glu Thr Met Ala Arg Cys Val Cys     930 935 940 Glu Leu Ser Pro His Glu Thr Val Ala Asn Pro Arg Leu Lys Asn Ser 945 950 955 960 Ile Ile Glu Asn His Gly Leu Lys Ser Ala Arg Ser Leu Gly Pro Gly                 965 970 975 Ser Ile Asn Ile Asn Ser Ser Asn Asp Ala Lys Lys Trp Asn Gln Gly             980 985 990 His Tyr Thr Thr Lys Leu Ala Leu Val Leu Cys Trp Phe Met Pro Ala         995 1000 1005 Lys Phe His Arg Phe Ile Trp Ala Ala Ile Ser Met Phe Arg Arg Lys    1010 1015 1020 Lys Met Met Val Asp Leu Arg Phe Leu Ala His Leu Ser Ser Lys Ser 1025 1030 1035 1040 Glu Ser Arg Ser Ser Asp Pro Phe Arg Glu Ala Met Thr Asp Ala Phe                1045 1050 1055 His Gly Asn Arg Glu Val Ser Trp Met Asp Lys Gly Arg Thr Tyr Ile            1060 1065 1070 Lys Thr Glu Thr Gly Met Met Gln Gly Ile Leu His Phe Thr Ser Ser        1075 1080 1085 Leu Leu His Ser Cys Val Gln Ser Phe Tyr Lys Ser Tyr Phe Val Ser    1090 1095 1100 Lys Leu Lys Glu Gly Tyr Met Gly Glu Ser Ile Ser Gly Val Val Asp 1105 1110 1115 1120 Val Ile Glu Gly Ser Asp Asp Ser Ala Ile Met Ile Ser Ile Arg Pro                1125 1130 1135 Lys Ser Asp Met Asp Glu Val Arg Ser Arg Phe Phe Val Ala Asn Leu            1140 1145 1150 Leu His Ser Val Lys Phe Leu Asn Pro Leu Phe Gly Ile Tyr Ser Ser        1155 1160 1165 Glu Lys Ser Thr Val Asn Thr Val Tyr Cys Val Glu Tyr Asn Ser Glu    1170 1175 1180 Phe His Phe His Arg His Leu Val Arg Pro Thr Leu Arg Trp Ile Ala 1185 1190 1195 1200 Ala Ser His Gln Ile Ser Glu Thr Glu Ala Leu Ala Ser Arg Gln Glu                1205 1210 1215 Asp Tyr Ser Asn Leu Leu Thr Gln Cys Leu Glu Gly Gly Ala Ser Phe            1220 1225 1230 Ser Leu Thr Tyr Leu Ile Gln Cys Ala Gln Leu Leu His His Tyr Met        1235 1240 1245 Leu Leu Gly Leu Cys Leu His Pro Leu Phe Gly Thr Phe Met Gly Met    1250 1255 1260 Leu Ile Ser Asp Pro Asp Pro Ala Leu Gly Phe Phe Leu Met Asp Asn 1265 1270 1275 1280 Pro Ala Phe Ala Gly Gly Ala Gly Phe Arg Phe Asn Leu Trp Arg Ala                1285 1290 1295 Cys Lys Thr Thr Asp Leu Gly Arg Lys Tyr Ala Tyr Tyr Phe Asn Glu            1300 1305 1310 Ile Gln Gly Lys Thr Lys Gly Asp Glu Asp Tyr Arg Ala Leu Asp Ala        1315 1320 1325 Thr Ser Gly Gly Thr Leu Ser His Ser Val Met Val Tyr Trp Gly Asp    1330 1335 1340 Arg Lys Lys Tyr Gln Ala Leu Leu Ser Arg Met Gly Leu Pro Glu Asp 1345 1350 1355 1360 Trp Val Glu Gln Ile Asp Glu Asn Pro Gly Val Leu Tyr Arg Arg Ala                1365 1370 1375 Ala Asn Lys Lys Glu Leu Leu Leu Lys Leu Ala Glu Lys Val His Ser            1380 1385 1390 Pro Gly Val Thr Ser Ser Leu Ser Lys Gly His Val Val Pro Arg Val        1395 1400 1405 Val Ala Ala Gly Val Tyr Leu Leu Ser Arg His Cys Phe Arg Phe Ser    1410 1415 1420 Ser Ser Ile His Gly Arg Gly Ser Thr Gln Lys Ala Ser Leu Ile Lys 1425 1430 1435 1440 Leu Leu Met Met Ser Ser Ile Ser Ala Met Lys His Gly Gly Ser Leu                1445 1450 1455 Asn Pro Asn Gln Glu Arg Met Leu Phe Pro Gln Ala Gln Glu Tyr Asp            1460 1465 1470 Arg Val Cys Thr Leu Leu Glu Glu Val Glu His Leu Thr Gly Lys Phe        1475 1480 1485 Val Val Arg Glu Arg Asn Ile Val Arg Ser Arg Ile Asp Leu Phe Gln    1490 1495 1500 Glu Pro Val Asp Leu Arg Cys Lys Ala Glu Asp Leu Val Ser Glu Val 1505 1510 1515 1520 Trp Phe Gly Leu Lys Arg Thr Lys Leu Gly Pro Arg Leu Leu Lys Glu                1525 1530 1535 Glu Trp Asp Lys Leu Arg Ala Ser Phe Ala Trp Leu Ser Thr Asp Pro            1540 1545 1550 Ser Glu Thr Leu Arg Asp Gly Pro Phe Leu Ser His Val Gln Phe Arg        1555 1560 1565 Asn Phe Ile Ala His Val Asp Ala Lys Ser Arg Ser Val Arg Leu Leu    1570 1575 1580 Gly Ala Pro Val Lys Lys Ser Gly Gly Val Thr Thr Ile Ser Gln Val 1585 1590 1595 1600 Val Arg Met Asn Phe Phe Pro Gly Phe Ser Leu Glu Ala Glu Lys Ser                1605 1610 1615 Leu Asp Asn Gln Glu Arg Leu Glu Ser Ile Ser Ile Leu Lys His Val            1620 1625 1630 Leu Phe Met Val Leu Asn Gly Pro Tyr Thr Glu Glu Tyr Lys Leu Glu        1635 1640 1645 Met Ile Ile Glu Ala Phe Ser Thr Leu Val Ile Pro Gln Pro Ser Glu    1650 1655 1660 Val Ile Arg Lys Ser Arg Thr Met Thr Leu Cys Leu Leu Ser Asn Tyr 1665 1670 1675 1680 Leu Ser Ser Arg Gly Gly Ser Ile Leu Asp Gln Ile Glu Arg Ala Gln                1685 1690 1695 Ser Gly Thr Leu Gly Gly Phe Ser Lys Pro Gln Lys Thr Phe Ile Arg            1700 1705 1710 Pro Gly Gly Gly Val Gly Tyr Lys Gly Lys Gly Val Trp Thr Gly Val        1715 1720 1725 Met Glu Asp Thr His Val Gln Ile Leu Ile Asp Gly Asp Gly Thr Ser    1730 1735 1740 Asn Trp Leu Glu Glu Ile Arg Leu Ser Ser Asp Ala Arg Leu Tyr Asp 1745 1750 1755 1760 Val Ile Glu Ser Ile Arg Arg Leu Cys Asp Asp Leu Gly Ile Asn Asn                1765 1770 1775 Arg Val Ala Ser Ala Tyr Arg Gly His Cys Met Val Arg Leu Ser Gly            1780 1785 1790 Phe Lys Ile Lys Pro Ala Ser Arg Thr Asp Gly Cys Pro Val Arg Ile        1795 1800 1805 Met Glu Arg Gly Phe Arg Ile Arg Glu Leu Gln Asn Pro Asp Glu Val    1810 1815 1820 Lys Met Arg Val Arg Gly Asp Ile Leu Asn Leu Ser Val Thr Ile Gln 1825 1830 1835 1840 Glu Gly Arg Val Met Asn Ile Leu Ser Tyr Arg Pro Arg Asp Thr Asp                1845 1850 1855 Ile Ser Glu Ser Ala Ala Ala Tyr Leu Trp Ser Asn Arg Asp Leu Phe            1860 1865 1870 Ser Phe Gly Lys Lys Glu Pro Ser Cys Ser Trp Ile Cys Leu Lys Thr        1875 1880 1885 Leu Asp Asn Trp Ala Trp Ser His Ala Ser Val Leu Leu Ala Asn Asp    1890 1895 1900 Arg Lys Thr Gln Gly Ile Asp Asn Arg Ala Met Gly Asn Ile Phe Arg 1905 1910 1915 1920 Asp Cys Leu Glu Gly Ser Leu Arg Lys Gln Gly Leu Met Arg Ser Lys                1925 1930 1935 Leu Thr Glu Met Val Glu Lys Asn Val Val Pro Leu Thr Thr Gln Glu            1940 1945 1950 Leu Val Asp Ile Leu Glu Glu Asp Ile Asp Phe Ser Asp Val Ile Ala        1955 1960 1965 Val Glu Leu Ser Glu Gly Ser Leu Asp Ile Glu Ser Ile Phe Asp Gly    1970 1975 1980 Ala Pro Ile Leu Trp Ser Ala Glu Val Glu Glu Phe Gly Glu Gly Val 1985 1990 1995 2000 Val Ala Val Ser Tyr Ser Ser Lys Tyr Tyr His Leu Thr Leu Met Asp                2005 2010 2015 Gln Ala Ala Ile Thr Met Cys Ala Ile Met Gly Lys Glu Gly Cys Arg            2020 2025 2030 Gly Leu Leu Thr Glu Lys Arg Cys Met Ala Ala Ile Arg Glu Gln Val        2035 2040 2045 Arg Pro Phe Leu Ile Phe Leu Gln Ile Pro Glu Asp Ser Ile Ser Trp    2050 2055 2060 Val Ser Asp Gln Phe Cys Asp Ser Arg Gly Leu Asp Glu Glu Ser Thr 2065 2070 2075 2080 Ile Met Trp Gly ***                2085 <210> 10 <211> 1074 <212> PRT <213> Unknown <220> <223> severe fever thrombocytopenia syndrome virus A type M <400> 10 Met Met Lys Val Ile Trp Phe Ser Ser Leu Ile Cys Leu Val Ile Gln   1 5 10 15 Cys Gly Gly Asp Thr Gly Pro Ile Ile Cys Ala Gly Pro Ile His Ser              20 25 30 Asn Lys Ser Ala Asp Ile Pro His Leu Leu Gly Tyr Ser Glu Lys Ile          35 40 45 Cys Gln Ile Asp Arg Leu Ile His Val Ser Ser Trp Leu Arg Asn His      50 55 60 Ser Gln Phe Gln Gly Tyr Val Gly Gln Arg Gly Gly Arg Ser Gln Val  65 70 75 80 Ser Tyr Tyr Pro Ala Glu Asn Ser Tyr Ser Arg Trp Ser Gly Leu Leu                  85 90 95 Ser Pro Cys Asp Ala Asp Trp Leu Gly Met Leu Val Val Lys Lys Ala             100 105 110 Lys Gly Ser Asp Met Ile Val Pro Gly Pro Ser Tyr Lys Gly Lys Val         115 120 125 Phe Phe Glu Arg Pro Thr Phe Asp Gly Tyr Val Gly Trp Gly Cys Gly     130 135 140 Ser Gly Lys Ser Arg Thr Glu Ser Gly Glu Leu Cys Ser Ser Asp Ser 145 150 155 160 Gly Thr Ser Ser Gly Leu Leu Pro Ser Asp Arg Val Leu Trp Ile Gly                 165 170 175 Asp Val Ala Cys Gln Pro Met Thr Pro Ile Pro Glu Glu Thr Phe Leu             180 185 190 Glu Leu Lys Ser Phe Ser Gln Ser Glu Phe Pro Asp Ile Cys Lys Ile         195 200 205 Asp Gly Ile Val Phe Asn Gln Cys Glu Gly Glu Ser Leu Pro Gln Pro     210 215 220 Phe Asp Val Ala Trp Met Asp Val Gly His Ser His Lys Ile Ile Met 225 230 235 240 Arg Glu His Lys Thr Lys Trp Val Gln Glu Ser Ser Ser Lys Asp Phe                 245 250 255 Val Cys Tyr Lys Glu Gly Thr Gly Pro Cys Ser Glu Ser Glu Glu Lys             260 265 270 Thr Cys Lys Thr Ser Gly Ser Cys Arg Gly Asp Met Gln Phe Cys Lys         275 280 285 Val Ala Gly Cys Glu His Gly Glu Glu Ala Ser Glu Ala Lys Cys Arg     290 295 300 Cys Ser Leu Val His Lys Pro Gly Glu Val Val Val Ser Tyr Gly Gly 305 310 315 320 Met Arg Val Arg Pro Lys Cys Tyr Gly Phe Ser Arg Met Met Ala Thr                 325 330 335 Leu Glu Val Asn Glu Pro Glu Gln Arg Asn Gly Gln Cys Thr Gly Cys             340 345 350 His Leu Glu Cys Ile Asn Gly Gly Val Arg Leu Ile Thr Leu Thr Ser         355 360 365 Glu Leu Lys Ser Ala Thr Val Cys Ala Ser His Phe Cys Ser Ser Ala     370 375 380 Thr Ser Gly Lys Lys Ser Thr Glu Ile Gln Phe His Ser Gly Ser Leu 385 390 395 400 Val Gly Lys Thr Ala Ile His Val Lys Gly Ala Leu Val Asp Gly Thr                 405 410 415 Glu Phe Thr Phe Glu Gly Ser Cys Met Phe Pro Asp Gly Cys Asp Ala             420 425 430 Val Asp Cys Thr Phe Cys Arg Glu Phe Leu Lys Asn Pro Gln Cys Tyr         435 440 445 Pro Ala Lys Lys Trp Leu Phe Ile Ile Ile Val Ile Leu Leu Gly Tyr     450 455 460 Ala Gly Leu Met Leu Leu Thr Asn Val Leu Lys Ala Ile Gly Val Trp 465 470 475 480 Gly Ser Trp Val Ile Ala Pro Val Lys Leu Val Phe Ala Ile Ile Lys                 485 490 495 Lys Leu Met Arg Ala Val Ser Cys Leu Met Gly Lys Leu Met Asp Arg             500 505 510 Gly Arg Gln Val Ile His Glu Glu Ile Gly Glu Asn Arg Glu Gly Asn         515 520 525 Gln Asp Asp Val Arg Ile Glu Met Ala Arg Pro Arg Arg Val Arg His     530 535 540 Trp Met Tyr Ser Pro Val Ile Leu Thr Ile Leu Ala Met Gly Leu Ala 545 550 555 560 Glu Gly Cys Asp Glu Met Val His Ala Asp Ser Lys Leu Val Ser Cys                 565 570 575 Arg Gln Gly Ser Gly Asn Met Lys Glu Cys Val Thr Thr Gly Arg Ala             580 585 590 Leu Leu Pro Ala Val Asn Pro Gly Gln Glu Ala Cys Leu His Phe Thr         595 600 605 Ala Pro Gly Ser Pro Asp Ser Lys Cys Leu Lys Ile Lys Val Lys Arg     610 615 620 Ile Asn Leu Lys Cys Lys Lys Ser Ser Ser Tyr Phe Val Pro Asp Ala 625 630 635 640 Arg Ser Arg Cys Thr Ser Val Arg Arg Cys Arg Trp Ala Gly Asp Cys                 645 650 655 Gln Ser Gly Cys Pro Pro His Phe Thr Ser Asn Ser Phe Ser Asp Asp             660 665 670 Trp Ala Gly Lys Met Asp Arg Ala Gly Leu Gly Phe Ser Gly Cys Ser         675 680 685 Asp Gly Cys Gly Gly Ala Ala Cys Gly Cys Phe Asn Ala Ala Pro Ser     690 695 700 Cys Ile Phe Trp Arg Lys Trp Val Glu Asn Pro His Gly Ile Ile Trp 705 710 715 720 Lys Val Ser Pro Cys Ala Ala Trp Val Pro Ser Ala Val Ile Glu Leu                 725 730 735 Thr Met Pro Ser Gly Glu Val Arg Thr Phe His Pro Met Ser Gly Ile             740 745 750 Pro Thr Gln Val Phe Lys Gly Val Ser Val Thr Tyr Leu Gly Ser Asp         755 760 765 Met Glu Val Ser Gly Leu Thr Asp Leu Cys Glu Ile Glu Glu Leu Lys     770 775 780 Ser Lys Lys Leu Ala Leu Ala Pro Cys Asn Gln Ala Gly Met Gly Val 785 790 795 800 Val Gly Lys Val Gly Glu Ile Gln Cys Ser Ser Glu Glu Ser Ala Arg                 805 810 815 Thr Ile Lys Lys Asp Gly Cys Ile Trp Asn Ala Asp Leu Val Gly Ile             820 825 830 Glu Leu Arg Val Asp Asp Ala Val Cys Tyr Ser Lys Ile Thr Ser Val         835 840 845 Glu Ala Val Ala Asn Tyr Ser Ala Ile Pro Thr Thr Ile Gly Gly Leu     850 855 860 Arg Phe Glu Arg Ser His Asp Ser Gln Gly Lys Ile Ser Gly Ser Pro 865 870 875 880 Leu Asp Ile Thr Ala Ile Arg Gly Ser Phe Ser Ile Asn Tyr Arg Gly                 885 890 895 Leu Arg Leu Ser Leu Ser Glu Ile Thr Ala Thr Cys Thr Gly Glu Val             900 905 910 Thr Asn Val Ser Gly Cys Tyr Ser Cys Met Thr Gly Ala Lys Val Ser         915 920 925 Ile Lys Leu His Ser Ser Lys Asn Ser Thr Ala His Val Arg Cys Lys     930 935 940 Gly Asp Glu Thr Ala Phe Ser Val Leu Glu Gly Val His Ser Tyr Ser 945 950 955 960 Val Ser Leu Ser Phe Asp His Ala Val Val Asp Glu Gln Cys Gln Leu                 965 970 975 Asn Cys Gly Gly His Glu Ser Gln Val Thr Leu Arg Gly Asn Leu Ile             980 985 990 Phe Leu Asp Val Pro Lys Phe Val Asp Gly Ser Tyr Met Gln Thr Tyr         995 1000 1005 His Ser Thr Val Pro Thr Gly Ala Asn Ile Pro Ser Pro Thr Asp Trp    1010 1015 1020 Leu Asn Ala Leu Phe Gly Asn Gly Leu Ser Arg Trp Ile Leu Gly Val 1025 1030 1035 1040 Ile Gly Val Leu Leu Gly Gly Leu Ala Leu Phe Phe Leu Ile Met Ser                1045 1050 1055 Leu Phe Lys Leu Gly Thr Lys Gln Val Phe Arg Ser Arg Thr Lys Leu            1060 1065 1070 Ala ***         <210> 11 <211> 246 <212> PRT <213> Unknown <220> <223> severe fever thrombocytopenia syndrome virus A type NP <400> 11 Met Ser Glu Trp Ser Arg Ile Ala Val Glu Phe Gly Glu Gln Gln Leu   1 5 10 15 Asn Leu Thr Glu Leu Glu Asp Phe Ala Arg Glu Leu Ala Tyr Glu Gly              20 25 30 Leu Asp Pro Ala Leu Ile Ile Lys Lys Leu Lys Glu Thr Gly Gly Asp          35 40 45 Asp Trp Val Lys Asp Thr Lys Phe Ile Ile Val Phe Ala Leu Thr Arg      50 55 60 Gly Asn Lys Ile Val Lys Ala Ser Gly Lys Met Ser Asn Ser Gly Ser  65 70 75 80 Lys Arg Leu Met Ala Leu Gln Glu Lys Tyr Gly Leu Val Glu Arg Ala                  85 90 95 Glu Thr Arg Leu Ser Ile Thr Pro Val Arg Val Ala Gln Ser Leu Pro             100 105 110 Thr Trp Thr Cys Ala Ala Ala Ala Ala Leu Lys Glu Tyr Leu Pro Val         115 120 125 Gly Pro Ala Val Met Asn Leu Lys Val Glu Asn Tyr Pro Pro Glu Met     130 135 140 Met Cys Met Ala Phe Gly Ser Leu Ile Pro Thr Ala Gly Val Ser Glu 145 150 155 160 Ala Thr Thr Lys Thr Leu Met Glu Ala Tyr Ser Leu Trp Gln Asp Ala                 165 170 175 Phe Thr Lys Thr Ile Asn Val Lys Met Arg Gly Ala Ser Lys Thr Glu             180 185 190 Val Tyr Asn Ser Phe Arg Asp Pro Leu His Ala Ala Val Asn Ser Val         195 200 205 Phe Phe Pro Asn Asp Val Arg Val Lys Trp Leu Lys Ala Lys Gly Ile     210 215 220 Leu Gly Pro Asp Gly Val Pro Ser Arg Ala Ala Glu Val Ala Ala Ala 225 230 235 240 Ala Tyr Arg Asn Leu ***                 245 <210> 12 <211> 294 <212> PRT <213> Unknown <220> <223> severe fever thrombocytopenia syndrome virus A type NS <400> 12 Met Ser Leu Ser Lys Cys Ser Asn Val Asp Leu Lys Ser Val Ala Met   1 5 10 15 Asn Ala Asn Thr Val Arg Leu Glu Pro Ser Leu Gly Glu Tyr Pro Thr              20 25 30 Leu Arg Arg Asp Leu Val Glu Cys Ser Cys Ser Val Leu Thr Leu Ser          35 40 45 Met Val Lys Arg Met Gly Lys Met Thr Asn Thr Val Trp Leu Phe Gly      50 55 60 Asn Pro Lys Asn Pro Leu His Gln Leu Glu Pro Gly Leu Glu Gln Leu  65 70 75 80 Leu Asp Met Tyr Tyr Lys Asp Met Arg Cys Tyr Ser Gln Arg Glu Leu                  85 90 95 Ser Ala Leu Arg Trp Pro Ser Gly Lys Pro Ser Val Trp Phe Leu Gln             100 105 110 Ala Ala His Met Phe Phe Ser Ile Lys Asn Ser Trp Ala Met Glu Thr         115 120 125 Gly Arg Glu Asn Trp Arg Gly Leu Phe His Arg Ile Thr Lys Gly Gln     130 135 140 Lys Tyr Leu Phe Glu Gly Asp Met Ile Leu Asp Ser Leu Glu Ala Ile 145 150 155 160 Glu Lys Arg Arg Leu Arg Leu Gly Leu Pro Glu Ile Leu Ile Thr Gly                 165 170 175 Leu Ser Pro Ile Leu Asp Val Ala Leu Leu Gln Ile Glu Ser Leu Ala             180 185 190 Arg Leu Arg Gly Met Ser Leu Asn His His Leu Phe Thr Ser Ser Ser         195 200 205 Leu Arg Lys Pro Leu Leu Asp Cys Trp Asp Phe Phe Ile Pro Ile Arg     210 215 220 Lys Lys Lys Thr Asp Gly Ser Tyr Ser Val Leu Asp Glu Asp Asp Glu 225 230 235 240 Pro Gly Val Leu Gln Gly Tyr Pro Tyr Leu Met Ala His Tyr Leu Asn                 245 250 255 Arg Cys Pro Phe His Asn Leu Ile Arg Phe Asp Glu Glu Leu Arg Thr             260 265 270 Ala Ala Leu Asn Thr Ile Trp Gly Arg Asp Trp Pro Ala Ile Gly Asp         275 280 285 Leu Pro Lys Glu Val ***     290 <210> 13 <211> 2085 <212> PRT <213> Unknown <220> <223> severe fever thrombocytopenia syndrome virus F type L <400> 13 Met Asp Leu Glu Val Leu Cys Gly Arg Ile Asn Val Glu Asn Gly Leu   1 5 10 15 Ser Leu Gly Glu Pro Gly Leu Tyr Asp Gln Ile Tyr Asp Arg Pro Gly              20 25 30 Leu Pro Asp Leu Asp Val Thr Val Asp Ala Thr Gly Val Thr Val Asp          35 40 45 Ile Gly Ala Val Pro Asp Ser Ala Ser Gln Leu Gly Ser Ser Ile Asn      50 55 60 Ala Gly Leu Ile Thr Ile Gln Leu Ser Glu Ala Tyr Lys Ile Asn His  65 70 75 80 Asp Phe Thr Phe Ser Gly Leu Ser Lys Thr Thr Asp Arg Arg Leu Ser                  85 90 95 Glu Val Phe Pro Ile Thr His Asp Gly Ser Asp Gly Met Thr Pro Asp             100 105 110 Val Ile His Thr Arg Leu Asp Gly Thr Ile Val Val Val Glu Phe Ser         115 120 125 Thr Thr Arg Ser His Asn Ile Gly Gly Leu Glu Ala Ala Tyr Arg Thr     130 135 140 Lys Ile Glu Lys Tyr Arg Asp Pro Ile Ser Arg Arg Val Asp Ile Met 145 150 155 160 Glu Asn Pro Arg Val Phe Phe Gly Val Ile Val Val Ser Ser Gly Gly                 165 170 175 Val Leu Ser Asn Met Pro Leu Thr Gln Asp Glu Ala Glu Glu Leu Met             180 185 190 Tyr Arg Phe Cys Ile Ala Asn Glu Ile Tyr Thr Lys Ala Arg Ser Met         195 200 205 Asp Ala Asp Ile Glu Leu Gln Lys Ser Glu Glu Glu Leu Glu Ala Ile     210 215 220 Ser Arg Ala Leu Ser Phe Phe Ser Leu Phe Glu Pro Asn Ile Glu Arg 225 230 235 240 Val Glu Gly Thr Phe Pro Asn Ser Glu Ile Glu Met Leu Glu Gln Phe                 245 250 255 Leu Ser Thr Pro Ala Asp Val Asp Phe Ile Thr Lys Thr Leu Lys Ala             260 265 270 Lys Glu Val Glu Ala Tyr Ala Asp Leu Cys Asp Ser His Tyr Leu Lys         275 280 285 Pro Glu Lys Thr Ile Gln Glu Arg Leu Glu Ile Asn Arg Cys Glu Ala     290 295 300 Ile Asp Lys Thr Gln Asp Leu Leu Ala Gly Leu His Ala Arg Ser Asn 305 310 315 320 Lys Gln Thr Ser Leu Asn Arg Gly Thr Val Lys Leu Pro Pro Trp Leu                 325 330 335 Pro Lys Pro Ser Ser Glu Ser Ile Asp Ile Lys Thr Asp Ser Gly Phe             340 345 350 Gly Ser Leu Met Asp His Gly Ala Tyr Gly Glu Leu Trp Ala Lys Cys         355 360 365 Leu Leu Asp Val Ser Leu Gly Asn Val Glu Gly Val Val Ser Asp Pro     370 375 380 Ala Lys Glu Leu Asp Ile Ala Ile Ser Asp Asp Pro Glu Lys Asp Thr 385 390 395 400 Pro Lys Glu Ala Lys Ile Thr Tyr Arg Arg Phe Lys Pro Ala Leu Ser                 405 410 415 Ser Ser Ala Arg Gln Glu Phe Ser Leu Gln Gly Val Glu Gly Lys Lys             420 425 430 Trp Lys Arg Met Ala Ala Asn Gln Lys Lys Glu Lys Glu Ser His Glu         435 440 445 Thr Leu Ser Pro Phe Leu Asp Val Asp Asp Ile Gly Asp Phe Leu Thr     450 455 460 Phe Asn Asn Leu Leu Ala Asp Ser Arg Tyr Gly Asp Glu Ser Ile Gln 465 470 475 480 Arg Ala Val Ser Ile Leu Leu Glu Lys Ala Ser Ala Met Gln Asp Thr                 485 490 495 Glu Leu Thr His Ala Leu Asn Asp Ser Phe Lys Arg Asn Leu Ser Ser             500 505 510 Asn Val Val Gln Trp Ser Leu Trp Val Ser Cys Leu Ala Gln Glu Leu         515 520 525 Ala Ser Ala Leu Lys Gln His Cys Arg Ala Gly Glu Phe Ile Ile Lys     530 535 540 Lys Leu Lys Phe Trp Pro Ile Tyr Val Ile Ile Lys Pro Thr Lys Ser 545 550 555 560 Ser Ser His Ile Phe Tyr Ser Leu Gly Ile Arg Lys Ala Asp Val Thr                 565 570 575 Arg Arg Leu Thr Gly Arg Val Phe Ser Asp Thr Ile Asp Ala Gly Glu             580 585 590 Trp Glu Leu Thr Glu Phe Lys Ser Leu Lys Thr Cys Lys Leu Thr Asn         595 600 605 Leu Val Asn Leu Pro Cys Thr Met Leu Asn Ser Ile Ala Phe Trp Arg     610 615 620 Glu Lys Leu Gly Val Ala Pro Trp Leu Val Arg Lys Pro Cys Ser Glu 625 630 635 640 Leu Arg Glu Gln Val Gly Leu Thr Phe Leu Val Ser Leu Glu Asp Lys                 645 650 655 Ser Lys Thr Glu Glu Ile Ile Thr Leu Thr Arg Tyr Thr Gln Met Glu             660 665 670 Gly Phe Val Ser Pro Pro Met Leu Pro Lys Pro Gln Lys Met Leu Gly         675 680 685 Lys Leu Glu Gly Pro Leu Arg Thr Lys Leu Gln Val Tyr Leu Leu Arg     690 695 700 Lys His Leu Asp Cys Met Val Arg Ile Ala Ser Gln Pro Phe Ser Leu 705 710 715 720 Ile Pro Arg Glu Gly Arg Val Glu Trp Gly Gly Thr Phe His Ala Ile                 725 730 735 Ser Gly Arg Ser Thr Asn Leu Glu Asn Met Val Asn Ser Trp Tyr Ile             740 745 750 Gly Tyr Tyr Lys Asn Lys Glu Glu Ser Thr Glu Leu Asn Ala Leu Gly         755 760 765 Glu Met Tyr Lys Lys Ile Val Glu Met Glu Glu Asp Lys Pro Ser Ser     770 775 780 Pro Glu Phe Leu Gly Trp Gly Asp Thr Asp Ser Pro Lys Lys His Glu 785 790 795 800 Phe Ser Arg Ser Phe Leu Arg Ala Ala Cys Ser Ser Leu Glu Arg Glu                 805 810 815 Ile Ala Gln Arg His Gly Arg Gln Trp Lys Gln Asn Leu Glu Glu Arg             820 825 830 Val Leu Arg Glu Ile Gly Ala Lys Asn Ile Leu Asp Leu Ala Ser Met         835 840 845 Lys Ala Thr Ser Asn Phe Ser Lys Asp Trp Glu Leu Tyr Ser Glu Val     850 855 860 Gln Thr Lys Glu Tyr His Arg Ser Lys Leu Leu Glu Lys Met Ala Thr 865 870 875 880 Leu Ile Glu Lys Gly Val Met Trp Tyr Ile Asp Ala Val Gly Gln Ala                 885 890 895 Trp Lys Ala Val Leu Asp Asp Gly Cys Met Arg Ile Cys Leu Phe Lys             900 905 910 Lys Asn Gln His Gly Gly Leu Arg Glu Ile Tyr Val Met Asp Ala Asn         915 920 925 Ala Arg Leu Val Gln Phe Gly Val Glu Thr Met Ala Arg Cys Val Cys     930 935 940 Glu Leu Ser Pro His Glu Thr Val Ala Asn Pro Arg Leu Lys Asn Ser 945 950 955 960 Ile Ile Glu Asn His Gly Leu Lys Ser Ala Arg Ser Leu Gly Pro Gly                 965 970 975 Ser Ile Asn Ile Asn Ser Ser Asn Asp Ala Lys Lys Trp Asn Gln Gly             980 985 990 His Tyr Thr Thr Lys Leu Ala Leu Val Leu Cys Trp Phe Met Pro Ala         995 1000 1005 Lys Phe His Arg Phe Ile Trp Ala Ala Ile Ser Met Phe Arg Arg Lys    1010 1015 1020 Lys Met Met Val Asp Leu Arg Phe Leu Ala His Leu Ser Ser Lys Ser 1025 1030 1035 1040 Glu Ser Arg Ser Ser Asp Pro Phe Arg Glu Ala Met Thr Asp Ala Phe                1045 1050 1055 His Gly Asn Arg Asp Val Ser Trp Met Asp Lys Gly Arg Thr Tyr Ile            1060 1065 1070 Lys Thr Glu Thr Gly Met Met Gln Gly Ile Leu His Phe Thr Ser Ser        1075 1080 1085 Leu Leu His Ser Cys Val Gln Ser Phe Tyr Lys Ser Tyr Phe Val Ser    1090 1095 1100 Lys Leu Lys Glu Gly Tyr Met Gly Glu Ser Ile Ser Gly Val Val Asp 1105 1110 1115 1120 Val Ile Glu Gly Ser Asp Asp Ser Ala Ile Met Ile Ser Ile Arg Pro                1125 1130 1135 Lys Ser Asp Met Asp Glu Val Arg Ser Arg Phe Phe Val Ala Asn Leu            1140 1145 1150 Leu His Ser Val Lys Phe Leu Asn Pro Leu Phe Gly Ile Tyr Ser Ser        1155 1160 1165 Glu Lys Ser Thr Val Asn Thr Val Tyr Cys Val Glu Tyr Asn Ser Glu    1170 1175 1180 Phe His Phe His Arg His Leu Val Arg Pro Thr Leu Arg Trp Ile Ala 1185 1190 1195 1200 Ala Ser His Gln Ile Ser Glu Thr Glu Ala Leu Ala Ser Arg Gln Glu                1205 1210 1215 Asp Tyr Ser Asn Leu Leu Thr Gln Cys Leu Glu Gly Gly Ala Ser Phe            1220 1225 1230 Ser Leu Thr Tyr Leu Ile Gln Cys Ala Gln Leu Leu His His Tyr Met        1235 1240 1245 Leu Leu Gly Leu Cys Leu His Pro Leu Phe Gly Thr Phe Met Gly Met    1250 1255 1260 Leu Ile Ser Asp Pro Asp Pro Ala Leu Gly Phe Phe Leu Met Asp Asn 1265 1270 1275 1280 Pro Ala Phe Ala Gly Gly Ala Gly Phe Arg Phe Asn Leu Trp Arg Ala                1285 1290 1295 Cys Lys Thr Thr Asp Leu Gly Arg Lys Tyr Ala Tyr Tyr Phe Asn Glu            1300 1305 1310 Ile Gln Gly Lys Thr Lys Gly Asp Glu Asp Tyr Arg Ala Leu Asp Ala        1315 1320 1325 Thr Ser Gly Gly Thr Leu Ser His Ser Val Met Val Tyr Trp Gly Asp    1330 1335 1340 Arg Lys Lys Tyr Gln Ala Leu Leu Asn Arg Met Gly Leu Pro Glu Asp 1345 1350 1355 1360 Trp Val Glu Gln Ile Asp Glu Asn Pro Gly Val Leu Tyr Arg Arg Ala                1365 1370 1375 Ala Asn Lys Lys Glu Leu Leu Leu Lys Leu Ala Glu Lys Val His Ser            1380 1385 1390 Pro Gly Val Thr Ser Ser Leu Ser Lys Gly His Val Val Pro Arg Val        1395 1400 1405 Val Ala Ala Gly Val Tyr Leu Leu Ser Arg His Cys Phe Arg Phe Ser    1410 1415 1420 Ser Ser Ile His Gly Arg Gly Ser Thr Gln Lys Ala Ser Leu Ile Lys 1425 1430 1435 1440 Leu Leu Met Met Ser Ser Ile Ser Ala Met Lys His Gly Gly Ser Leu                1445 1450 1455 Asn Pro Asn Gln Glu Arg Met Leu Phe Pro Gln Ala Gln Glu Tyr Asp            1460 1465 1470 Arg Val Cys Thr Leu Leu Glu Glu Val Glu His Leu Thr Gly Lys Phe        1475 1480 1485 Val Val Arg Glu Arg Asn Ile Val Arg Ser Arg Ile Asp Leu Phe Gln    1490 1495 1500 Glu Pro Val Asp Leu Arg Cys Lys Ala Glu Asp Leu Val Ser Glu Val 1505 1510 1515 1520 Trp Phe Gly Leu Lys Arg Thr Lys Leu Gly Pro Arg Leu Leu Lys Glu                1525 1530 1535 Glu Trp Asp Lys Leu Arg Ala Ser Phe Ala Trp Leu Ser Thr Asp Pro            1540 1545 1550 Ser Glu Thr Leu Arg Asp Gly Pro Phe Leu Ser His Val Gln Phe Arg        1555 1560 1565 Asn Phe Ile Ala His Val Asp Ala Lys Ser Arg Ser Val Arg Leu Leu    1570 1575 1580 Gly Ala Pro Val Lys Lys Ser Gly Gly Val Thr Thr Ile Ser Gln Val 1585 1590 1595 1600 Val Arg Met Asn Phe Phe Pro Gly Phe Ser Leu Glu Ala Glu Lys Ser                1605 1610 1615 Leu Asp Asn Gln Glu Arg Leu Glu Ser Ile Ser Ile Leu Lys His Val            1620 1625 1630 Leu Phe Met Val Leu Asn Gly Pro Tyr Thr Glu Glu Tyr Lys Leu Glu        1635 1640 1645 Met Ile Ile Glu Ala Phe Ser Thr Leu Val Ile Pro Gln Pro Ser Glu    1650 1655 1660 Val Ile Arg Lys Ser Arg Thr Met Thr Leu Cys Leu Leu Ser Asn Tyr 1665 1670 1675 1680 Leu Ser Ser Arg Gly Gly Ser Ile Leu Asp Gln Ile Glu Arg Ala Gln                1685 1690 1695 Ser Gly Thr Leu Gly Gly Phe Ser Lys Pro Gln Lys Thr Phe Ile Arg            1700 1705 1710 Pro Gly Gly Gly Val Gly Tyr Lys Gly Lys Gly Val Trp Thr Gly Val        1715 1720 1725 Met Glu Asp Thr His Val Gln Ile Leu Ile Asp Gly Asp Gly Thr Ser    1730 1735 1740 Asn Trp Leu Glu Glu Ile Arg Leu Ser Ser Asp Ala Arg Leu Tyr Asp 1745 1750 1755 1760 Val Ile Glu Ser Ile Arg Arg Leu Cys Asp Asp Leu Gly Ile Asn Asn                1765 1770 1775 Arg Val Ala Ser Ala Tyr Arg Gly His Cys Met Val Arg Leu Ser Gly            1780 1785 1790 Phe Lys Ile Lys Pro Ala Ser Arg Thr Asp Gly Cys Pro Val Arg Ile        1795 1800 1805 Met Glu Arg Gly Phe Arg Ile Arg Glu Leu Gln Asn Pro Asp Glu Val    1810 1815 1820 Lys Met Arg Val Arg Gly Asp Ile Leu Asn Leu Ser Val Thr Ile Gln 1825 1830 1835 1840 Glu Gly Arg Val Met Asn Ile Leu Ser Tyr Arg Pro Arg Asp Thr Asp                1845 1850 1855 Ile Ser Glu Ser Ala Ala Ala Tyr Leu Trp Ser Asn Arg Asp Leu Phe            1860 1865 1870 Ser Phe Gly Lys Lys Glu Pro Ser Cys Ser Trp Ile Cys Leu Lys Thr        1875 1880 1885 Leu Asp Asn Trp Ala Trp Ser His Ala Ser Val Leu Leu Ala Asn Asp    1890 1895 1900 Arg Lys Thr Gln Gly Ile Asp Asn Arg Ala Met Gly Asn Ile Phe Arg 1905 1910 1915 1920 Asp Cys Leu Glu Gly Ser Leu Arg Lys Gln Gly Leu Met Arg Ser Lys                1925 1930 1935 Leu Thr Glu Met Val Glu Lys Asn Val Val Pro Leu Thr Thr Gln Glu            1940 1945 1950 Leu Val Asp Ile Leu Glu Glu Asp Ile Asp Phe Ser Asp Val Ile Ala        1955 1960 1965 Val Glu Leu Ser Glu Gly Ser Leu Asp Ile Glu Ser Ile Phe Asp Gly    1970 1975 1980 Ala Pro Ile Leu Trp Ser Ala Glu Val Glu Glu Phe Gly Glu Gly Val 1985 1990 1995 2000 Val Ala Val Ser Tyr Ser Ser Lys Tyr Tyr His Leu Thr Leu Met Asp                2005 2010 2015 Gln Ala Ala Ile Thr Met Cys Ala Ile Met Gly Lys Glu Gly Cys Arg            2020 2025 2030 Gly Leu Leu Thr Glu Lys Arg Cys Met Ala Ala Ile Arg Glu Gln Val        2035 2040 2045 Arg Pro Phe Leu Ile Phe Leu Gln Ile Pro Glu Asp Ser Ile Ser Trp    2050 2055 2060 Val Ser Asp Gln Phe Cys Asp Ser Arg Gly Leu Asp Glu Glu Ser Thr 2065 2070 2075 2080 Ile Met Trp Gly ***                2085 <210> 14 <211> 1074 <212> PRT <213> Unknown <220> <223> severe fever thrombocytopenia syndrome virus F type M <400> 14 Met Met Lys Val Ile Trp Phe Ser Ser Leu Ile Cys Phe Val Ile Gln   1 5 10 15 Cys Ser Gly Asp Ser Gly Pro Ile Ile Cys Ala Gly Pro Ile His Ser              20 25 30 Asn Lys Ser Ala Asp Ile Pro His Leu Leu Gly Tyr Ser Glu Lys Ile          35 40 45 Cys Gln Ile Asp Arg Leu Ile His Val Ser Ser Trp Leu Arg Asn His      50 55 60 Ser Gln Phe Gln Gly Tyr Val Gly Gln Arg Gly Gly Arg Ser Gln Val  65 70 75 80 Ser Tyr Tyr Pro Ala Glu Asn Ser Tyr Ser Arg Trp Ser Gly Leu Leu                  85 90 95 Ser Pro Cys Asp Ala Asp Trp Leu Gly Met Leu Val Val Lys Lys Ala             100 105 110 Lys Gly Ser Asp Met Ile Val Pro Gly Pro Ser Tyr Lys Gly Lys Val         115 120 125 Phe Phe Glu Arg Pro Thr Phe Asp Gly Tyr Val Gly Trp Gly Cys Gly     130 135 140 Ser Gly Lys Ser Arg Thr Glu Ser Gly Glu Leu Cys Ser Ser Asp Ser 145 150 155 160 Gly Thr Ser Ser Gly Leu Leu Pro Ser Asp Arg Val Leu Trp Ile Gly                 165 170 175 Asp Val Ala Cys Gln Pro Met Thr Pro Ile Pro Glu Glu Thr Phe Leu             180 185 190 Glu Leu Lys Ser Phe Ser Gln Ser Glu Phe Pro Asp Ile Cys Lys Ile         195 200 205 Asp Gly Ile Val Phe Asn Gln Cys Glu Gly Glu Ser Leu Pro Gln Pro     210 215 220 Phe Asp Val Ala Trp Met Asp Val Gly His Ser His Lys Ile Ile Met 225 230 235 240 Arg Glu His Lys Thr Lys Trp Val Gln Glu Ser Ser Ser Lys Asp Phe                 245 250 255 Val Cys Tyr Lys Glu Gly Thr Gly Pro Cys Ser Glu Ser Glu Glu Lys             260 265 270 Thr Cys Lys Thr Ser Gly Ser Cys Arg Gly Asp Met Gln Phe Cys Lys         275 280 285 Val Ala Gly Cys Glu His Gly Glu Glu Ala Ser Glu Ala Lys Cys Arg     290 295 300 Cys Ser Leu Val His Lys Pro Gly Glu Val Val Val Ser Tyr Gly Gly 305 310 315 320 Met Arg Val Arg Pro Lys Cys Tyr Gly Phe Ser Arg Met Met Ala Thr                 325 330 335 Leu Glu Val Asn Gln Pro Glu Gln Arg Ile Gly Gln Cys Thr Gly Cys             340 345 350 His Leu Glu Cys Ile Asn Gly Gly Val Arg Leu Ile Thr Leu Thr Ser         355 360 365 Glu Leu Lys Ser Ala Thr Val Cys Ala Ser His Phe Cys Ser Ser Ala     370 375 380 Thr Ser Gly Lys Lys Ser Thr Glu Ile Gln Phe His Ser Gly Ser Leu 385 390 395 400 Val Gly Lys Thr Ala Ile His Val Lys Gly Ala Leu Val Asp Gly Thr                 405 410 415 Glu Phe Thr Phe Glu Gly Ser Cys Met Phe Pro Asp Gly Cys Asp Ala             420 425 430 Val Asp Cys Thr Phe Cys Arg Glu Phe Leu Lys Asn Pro Gln Cys Tyr         435 440 445 Pro Ala Lys Lys Trp Leu Phe Ile Ile Ile Val Ile Leu Leu Gly Tyr     450 455 460 Ala Gly Leu Met Leu Leu Thr Asn Val Leu Lys Ala Ile Gly Ile Trp 465 470 475 480 Gly Ser Trp Val Ile Ala Pro Val Lys Leu Ile Phe Ala Ile Ile Lys                 485 490 495 Lys Leu Met Arg Thr Val Ser Cys Leu Met Gly Lys Leu Met Asp Arg             500 505 510 Gly Arg Gln Val Ile His Glu Glu Ile Gly Glu Asn Arg Glu Gly Asn         515 520 525 Gln Asp Asp Val Arg Ile Glu Met Ala Arg Pro Arg Arg Val Arg His     530 535 540 Trp Met Tyr Ser Pro Val Ile Leu Thr Ile Leu Ala Ile Gly Leu Ala 545 550 555 560 Glu Ser Cys Asp Glu Met Val His Ala Asp Ser Lys Leu Val Ser Cys                 565 570 575 Arg Gln Gly Ser Gly Asn Met Lys Glu Cys Val Thr Thr Gly Arg Ala             580 585 590 Leu Leu Pro Ala Val Asn Pro Gly Gln Glu Ala Cys Leu His Phe Thr         595 600 605 Ala Pro Gly Ser Pro Asp Ser Lys Cys Leu Lys Ile Lys Val Lys Arg     610 615 620 Ile Asn Leu Lys Cys Lys Lys Ser Ser Ser Tyr Phe Val Pro Asp Ala 625 630 635 640 Arg Ser Arg Cys Thr Ser Val Arg Arg Cys Arg Trp Ala Gly Asp Cys                 645 650 655 Gln Ser Gly Cys Pro Pro His Phe Thr Ser Asn Ser Phe Ser Asp Asp             660 665 670 Trp Ala Gly Lys Met Asp Arg Ala Gly Leu Gly Phe Ser Gly Cys Ser         675 680 685 Asp Gly Cys Gly Gly Ala Ala Cys Gly Cys Phe Asn Ala Ala Pro Ser     690 695 700 Cys Ile Phe Trp Arg Lys Trp Val Glu Asn Pro His Gly Ile Ile Trp 705 710 715 720 Lys Val Ser Pro Cys Ala Ala Trp Val Pro Ser Ala Val Ile Glu Leu                 725 730 735 Thr Met Pro Ser Gly Glu Val Arg Thr Phe His Pro Met Ser Gly Ile             740 745 750 Pro Thr Gln Val Phe Lys Gly Val Ser Val Thr Tyr Leu Gly Ser Asp         755 760 765 Met Glu Val Ser Gly Leu Thr Asp Leu Cys Glu Ile Glu Glu Leu Lys     770 775 780 Ser Lys Lys Leu Ala Leu Ala Pro Cys Asn Gln Ala Gly Met Gly Val 785 790 795 800 Val Gly Lys Val Gly Glu Ile Gln Cys Ser Ser Glu Glu Ser Ala Arg                 805 810 815 Thr Ile Lys Lys Asp Gly Cys Ile Trp Asn Ala Asp Leu Val Gly Ile             820 825 830 Glu Leu Arg Val Asp Asp Ala Val Cys Tyr Ser Lys Ile Thr Ser Val         835 840 845 Glu Ala Val Ala Asn Tyr Ser Ala Ile Pro Thr Thr Ile Gly Gly Leu     850 855 860 Arg Phe Glu Arg Ser His Asp Ser Gln Gly Lys Ile Ser Gly Ser Pro 865 870 875 880 Leu Asp Ile Thr Ala Ile Arg Gly Ser Phe Ser Val Asn Tyr Arg Gly                 885 890 895 Leu Arg Leu Ser Leu Ser Glu Ile Thr Ala Thr Cys Thr Gly Glu Val             900 905 910 Thr Asn Val Ser Gly Cys Tyr Ser Cys Met Thr Gly Ala Lys Val Ser         915 920 925 Ile Lys Leu His Ser Ser Lys Asn Ser Thr Ala His Val Arg Cys Lys     930 935 940 Gly Asp Glu Thr Ala Phe Ser Val Leu Glu Gly Val His Ser Tyr Thr 945 950 955 960 Val Asn Leu Ser Phe Asp His Ala Val Val Asp Glu Gln Cys Gln Leu                 965 970 975 Asn Cys Gly Gly His Glu Ser Gln Val Thr Leu Lys Gly Asn Leu Ile             980 985 990 Phe Leu Asp Val Pro Lys Phe Val Asp Gly Ser Tyr Met Gln Thr Tyr         995 1000 1005 His Ser Thr Val Pro Thr Gly Ala Asn Ile Pro Ser Pro Thr Asp Trp    1010 1015 1020 Leu Asn Ala Leu Phe Gly Asn Gly Leu Ser Arg Trp Ile Leu Gly Val 1025 1030 1035 1040 Ile Gly Val Leu Leu Gly Gly Leu Ala Leu Phe Phe Met Ile Met Ser                1045 1050 1055 Leu Phe Lys Leu Gly Thr Lys Gln Val Phe Arg Ser Arg Thr Lys Leu            1060 1065 1070 Ala ***         <210> 15 <211> 246 <212> PRT <213> Unknown <220> <223> severe fever thrombocytopenia syndrome virus F type NP <400> 15 Met Ser Glu Trp Ser Arg Ile Ala Val Glu Phe Gly Glu Gln Gln Leu   1 5 10 15 Asn Leu Thr Glu Leu Glu Asp Phe Ala Arg Glu Leu Ala Tyr Glu Gly              20 25 30 Leu Asp Pro Ala Leu Ile Ile Lys Lys Leu Lys Glu Thr Gly Gly Asp          35 40 45 Asp Trp Val Lys Asp Thr Lys Phe Ile Ile Val Phe Ala Leu Thr Arg      50 55 60 Gly Asn Lys Ile Val Lys Ala Ser Gly Lys Met Ser Asn Ser Gly Ser  65 70 75 80 Lys Arg Leu Met Ala Leu Gln Glu Lys Tyr Gly Leu Val Glu Arg Ala                  85 90 95 Glu Thr Arg Leu Ser Ile Thr Pro Val Arg Val Ala Gln Ser Leu Pro             100 105 110 Thr Trp Thr Cys Ala Ala Ala Ala Ala Leu Lys Glu Tyr Leu Pro Val         115 120 125 Gly Pro Ala Val Met Asn Leu Lys Val Glu Asn Tyr Pro Pro Glu Met     130 135 140 Met Cys Met Ala Phe Gly Ser Leu Ile Pro Thr Ala Gly Val Ser Glu 145 150 155 160 Ala Thr Thr Lys Thr Leu Met Glu Ala Tyr Ser Leu Trp Gln Asp Ala                 165 170 175 Phe Thr Lys Thr Ile Asn Val Lys Met Arg Gly Ala Ser Lys Thr Glu             180 185 190 Val Tyr Asn Ser Phe Arg Asp Pro Leu His Ala Ala Val Asn Ser Val         195 200 205 Phe Phe Pro Asn Asp Val Arg Val Lys Trp Leu Lys Ala Lys Gly Ile     210 215 220 Leu Gly Pro Asp Gly Val Pro Ser Arg Ala Ala Glu Val Ala Ala Ala 225 230 235 240 Ala Tyr Arg Asn Leu ***                 245 <210> 16 <211> 294 <212> PRT <213> Unknown <220> <223> severe fever thrombocytopenia syndrome virus F type NS <400> 16 Met Ser Leu Ser Lys Cys Ser Asn Val Asp Leu Lys Ser Val Ala Met   1 5 10 15 Asn Ala Asn Thr Val Arg Leu Glu Pro Ser Leu Gly Glu Tyr Pro Thr              20 25 30 Leu Arg Arg Asp Leu Val Glu Cys Ser Cys Ser Val Leu Thr Leu Ser          35 40 45 Met Val Lys Arg Met Gly Lys Met Thr Asn Thr Val Trp Leu Phe Gly      50 55 60 Asn Pro Lys Asn Pro Leu His Gln Leu Glu Pro Gly Leu Glu Gln Leu  65 70 75 80 Leu Asp Met Tyr Tyr Lys Asp Met Arg Cys Tyr Ser Gln Arg Glu Leu                  85 90 95 Ser Ala Leu Arg Trp Pro Ser Gly Lys Pro Ser Val Trp Phe Leu Gln             100 105 110 Ala Ala His Met Phe Phe Ser Ile Lys Asn Ser Trp Ala Met Glu Thr         115 120 125 Gly Arg Glu Asn Trp Arg Gly Leu Phe His Arg Ile Thr Lys Gly Arg     130 135 140 Arg Tyr Leu Phe Glu Gly Asp Met Ile Leu Asp Ser Leu Glu Ala Ile 145 150 155 160 Glu Lys Arg Arg Leu Arg Leu Gly Leu Pro Asp Ile Leu Ile Thr Gly                 165 170 175 Leu Ser Pro Ile Leu Asp Val Ala Leu Leu Gln Ile Glu Ser Leu Ala             180 185 190 Arg Leu Arg Gly Met Ser Leu Asn His His Leu Phe Thr Ser Ser Ser         195 200 205 Leu Arg Lys Pro Leu Leu Asp Cys Trp Asp Phe Phe Ile Pro Ile Arg     210 215 220 Lys Lys Lys Thr Asp Gly Ser Tyr Ser Val Leu Asp Glu Asp Asp Glu 225 230 235 240 Pro Gly Val Leu Gln Gly Tyr Pro Tyr Leu Met Ala His Tyr Leu Asn                 245 250 255 Arg Cys Pro Phe His Asn Leu Ile Arg Phe Asp Glu Glu Leu Arg Thr             260 265 270 Ala Ala Leu Asn Thr Ile Trp Gly Arg Asp Trp Pro Ala Ile Gly Asp         275 280 285 Pro Pro Lys Glu Val ***     290

Claims (13)

The amino acid No. 1061 of the protein expressed in the ORF (6255bp) of the L gene is glutamate, the 18th amino acid of the protein expressed in the ORF (3222bp) of the M gene is glycine, the 562th amino acid is glycine, the 960th amino acid is serine, 988 Severe fever thrombocytopenia, wherein the first amino acid is arginine or the 1053 amino acid is leucine, and the 145th amino acid of protein NS (294aa) expressed in the OR gene (1674 bp) of the S gene is lysine or glutamate of the 171th amino acid. syndrome virus, SFTSV). According to claim 1, L gene comprising the nucleotide sequence of SEQ ID NO: 1, M gene comprising the nucleotide sequence of SEQ ID NO: 2, S (NP) gene comprising the nucleotide sequence of SEQ ID NO: 3 and the base of SEQ ID NO: 4 A hyperthermic thrombocytopenia virus comprising an S (NS) gene comprising a sequence. Aspartic acid is amino acid 1061 of the protein expressed in the ORF (6255bp) of the L gene, 18th amino acid serine, 562th amino acid serine, 960th amino acid is threonine of the protein expressed in ORF (3222bp) of the M gene, Hyperthyroidal thrombocytopenia virus wherein the 988th amino acid is lysine or the 1053th amino acid is methionine, the 145th amino acid of protein NS (294aa) expressed in the ORF of the S gene (294aa) is arginine or the 171th amino acid is aspartic acid. According to claim 3, L gene comprising the nucleotide sequence of SEQ ID NO: 5, M gene containing the nucleotide sequence of SEQ ID NO: 6, S (NP) gene comprising the nucleotide sequence of SEQ ID NO: 7 and the base of SEQ ID NO: 8 A hyperthermic thrombocytopenia virus comprising an S (NS) gene comprising a sequence. An immunogenic composition for the prophylaxis or treatment of hyperthermic thrombocytopenia comprising any one of claims 1 to 4 as an active ingredient. 6. The immunogenic composition of claim 5, comprising inactivated mesophilic thrombocytopenia virus and a pharmaceutically acceptable carrier or adjuvant. 6. The form of claim 5, wherein the form of the immunogenic composition consists of a subunit vaccine, a vector vaccine, a chimeric vaccine, a DNA and an RNA vaccine produced using genes of live venom vaccine, dead venom vaccine, attenuated mesophilic thrombocytopenia virus. A vaccine composition for the prophylaxis or treatment of hyperthermic thrombocytopenia selected from the group. According to claim 5, L gene comprising the nucleotide sequence of SEQ ID NO: 1, M gene comprising the nucleotide sequence of SEQ ID NO: 2, S (NP) gene comprising the nucleotide sequence of SEQ ID NO: 3 and the base of SEQ ID NO: 4 Mesophilic thrombocytopenia virus comprising an S (NS) gene comprising a sequence; And an L gene comprising the nucleotide sequence of SEQ ID NO: 5, an M gene comprising the nucleotide sequence of SEQ ID NO: 6, an S (NP) gene comprising the nucleotide sequence of SEQ ID NO: 7, and an S nucleotide sequence of SEQ ID NO: 8 Immunogenic composition for the prevention or treatment of hyperthermic thrombocytopenia comprising an (NS) gene as an active ingredient. An antibody produced in response to immunization with the virus of claim 1 or an antigen thereof. A diagnostic kit for a hyperthermic thrombocytopenia virus comprising the virus of claim 1 or an antigen thereof. (a) contacting a sample isolated from a sample with a virus of any one of claims 1-4 or an antigen thereof under conditions in which an antigen / antibody complex can be formed; And
(b) detecting a hyperthermic thrombocytopenia virus antibody comprising detecting antigen / antibody complex formation. (a) administering the virus of any one of claims 1 to 4 or an antigen thereof to a non-human animal in an amount effective to induce an immune response; And
(b) collecting antiserum or plasma containing the antibody against the hyperthermic thrombocytopenia virus. (a) contacting a sample isolated from a sample with the virus of any one of claims 1 to 4 or an antigen thereof to form an antigen-antibody complex; And
(b) detecting the formation of the complex, providing information regarding the diagnosis of hyperthermic thrombocytopenia.

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