WO1988008449A1 - Hiv related human retrovirus strain with cloned nucleotide sequence and applications thereof - Google Patents

Hiv related human retrovirus strain with cloned nucleotide sequence and applications thereof Download PDF

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WO1988008449A1
WO1988008449A1 PCT/SE1988/000218 SE8800218W WO8808449A1 WO 1988008449 A1 WO1988008449 A1 WO 1988008449A1 SE 8800218 W SE8800218 W SE 8800218W WO 8808449 A1 WO8808449 A1 WO 8808449A1
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virus
sbl
proteins
hiv
clone
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PCT/SE1988/000218
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English (en)
French (fr)
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Jan Albert
Gunnel Biberfeld
Eva Maria FENYÖ
Erling Norrby
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Statens Bakteriologiska Laboratorium (Sbl)
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
    • C07K16/10—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses from RNA viruses
    • C07K16/1036—Retroviridae, e.g. leukemia viruses
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/15011—Lentivirus, not HIV, e.g. FIV, SIV
    • C12N2740/15021—Viruses as such, e.g. new isolates, mutants or their genomic sequences
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/15011—Lentivirus, not HIV, e.g. FIV, SIV
    • C12N2740/15022—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes

Definitions

  • HIV Human immunodeficiency virus
  • AIDS acquired immunodeficiency syndrome
  • HIV is a nontransforming retrovirus with a genomic structure similar to that of members of the lentivirus subfamily (References 2, 3).
  • the envelope of lentiviruses contains a small and poorly glycosylated transmembrane protein and a large heavily glycosylated external protein (References 4-7). Both these proteins show an antigenic lability (Reference 8).
  • the differences in polypeptide composition of env gene products between strains of HIV involve up to 30% of the araino acids (References 9, 10). The impact of this variation requires evaluation in two different contexts. One of these concerns the use of the envelope protein or parts thereof as antigen in serological tests and the other the use of the same kind of products for active immune prophylaxis.
  • Antibodies to the glycoproteins are identified in essentially all infected persons, whereas antibodies to the core proteins tend to disappear with advancing disease (References 5-7). Although the large external glycoprotein of HIV isolates shows extensive antigenic variations sera from infected persons generally identify gp120 of HTLV-IIIB and other representative HIV strains (References 5-7). Exceptions to this rule are certain virus isolates from West Africa. Thus virus isolated from apparently healthy individuals in Senegal (HTLV-IV) (Reference 11) and from AIDS patients in Guinea Bissau and Cape Verde (LAV-II) (Reference 12) have glycoproteins that are antigenically distinct from the envelope proteins of strains isolated in North America, Europe and Central Africa. Further differences are found in the electrophoretic mobility of some of the structural components.
  • HIV related human retroviruses Infection with HIV related human retroviruses has so far mainly been demonstrated among patients from West Africa. However, it is reasonable to expect that these viruses will spread to other parts of the world. It will therefore be increasingly important to serologically identify not only persons infected with currently prevailing HIV strains, but also individuals exposed to HIV related human retroviruses of West African origin. Many persons infected with these viruses will be identified in HIV ELISA because of the cross reactions between the core proteins. However, this may not always be the case since e.g. both of the patients from whom LAV-II was isolated were negative in HIV ELISA (Reference 12). Thus there is a great need for serological tests which identify antibodies against HIV related viruses.
  • the task to develop a vaccine protective against AIDS has become further complicated by the identification of at least partly pathogenic HIV related human retroviruses in West Africa with unique glycoprotein immunogenicity.
  • the possibility to identify neutralizing epitopes in the envelope shared between HIV and HIV related human retroviruses seems small.
  • a future envelope vaccine may therefore have to be bivalent.
  • the present invention consists of
  • SBL-6669-85 SBL-6669 for short.
  • Our SBL-6669 material is a stable isolate which can be cultivated in several host cell lines and can be used in assays for the defection of antibody to HIV related human retroviruses and frequently also HIV in samples of body fluids.
  • the present invention provides HIV related human retrovirus SBL-6669.
  • SBL-6669 can be maintained for prolonged periods of time in both the T-cell line HUT 78 (Reference 14) and the monocyclic cell line U937 clone 2 (Reference 15) and a further feature of the present invention comprises U937 clone 2 cells harbouring our SBL-6669 virus. Serum collected from the patient from whom SBL-6669 virus was obtained reacted with HTLV-IIIB antigens in enzyme linked immunosorbent assay (ELISA), but the confirmatory WB test failed to show reactivity against gp41 and gpl20 of HTLV-IIIB although gag and pol gene products (p24, p55, p34) were identified.
  • ELISA enzyme linked immunosorbent assay
  • PBMC peripheral blood mononuclear cells
  • PHA stimulated PBMC from a healthy seronegative donor.
  • Particle associated reverse transscriptase (RT) activity was observed within 2 weeks.
  • Cocultivation of PBMC with HUT 78 cells yielded a continuously virus producing cell line showing typical multinucleated giant cells. This line has continued to produce virus for more than 6 months.
  • By cell free infection have also other cell lines, among them U937 clone 2 , been infected.
  • SBL-6669 was shown to be a probable member of the lentivirus family by:
  • SBL-6669 was shown to differ from the prototype HIV strain HTLV-IIIB by the absence of cross-reactions between the glycoproteins of the two viruses.
  • SBL-6669 exhibited properties closely related to the recently identified HIV related human retroviruses, LAV-II and HTLV-IV, as evidenced by complete cross-reaction in RIPA and Western blotting. However, SBL-6669 differs from HTLV-IV and LAV-II by the size of the structural proteins as determined by RIPA and Western blotting.
  • HTLV-IV was obtained from Dr. M. Essex. Serum from a healthy Gambian immigrant to Sweden was used as HTLV-IV reference serum. This serum had been shown by Dr. Essex (personal communication) to react with envelope and core proteins of HTLV-IV.
  • LAV-II LAV type II ROD, CNCM No. 1-532
  • LAV-II reference serum No. 5473
  • HTLV-IIIB was provided by Dr. R. Gallo, National Cancer Institute, Bethesda, Md and a selected high titer HTLV-IIIB positive serum from a healthy homosexual man was used as HIV reference serum.
  • the approximate molecular size of major proteins of HTLV-IV, LAV-II and SBL-6669 was determined in RIPA (Fig. 2) and WB (Fig. 3). Table 1 lists the approximate size of corresponding proteins of HTLV-IV, LAV-II, SBL-6669 and HTLV-IIIB.
  • the external glycoprotein had an approximate molecular size of 120 kD in all four virus strains. Although we observed small interstrain size variation these were not as pronounced as the previously reported differences between LAV-I and LAV-II (Reference 12). The presumed transmembrane glycoprotein was only observed effectively in WB tests. In all three West African virus strains a 30-35 kD broad band was observed.
  • SBL-6669 virus and antigens can among other things be used for detection of antibodies which react with SBL-6669.
  • the basis for the production of SBL-6669 is that we have succeeded to persistently infect certain tumour cell lines. U937 clone 2 cells and HUT 78 cells have become stable producers of virus. Other T4 + positive cell lines such as Jurkat and .CEM can also be persistently infected.
  • SBL-6669 virus is well suited for in vitro production of virus in several cell lines and other cell cultures.
  • SBL-6669 virus An alternative method for the production of SBL-6669 virus is to infect the cell line U937 clone 16. This cell line is highly sensitive to the cytopathic effect of the virus and is eventually killed, but very large amounts of virus are produced during a short period of time before the cells are killed.
  • a third possible method for the production of SBL-6669 and SBL-6669 derived proteins is to construct recombinant vectors comprising the complete or part of the genome of SBL-6669 and transfect this vector into suitable bacteria, fungi or cells.
  • One way of constructing the recombinant vector is briefly to isolate unintegrated or integrated viral DNA from SBL-6669 infected cells, to cleave the latter form of DNA with a restriction enzyme to obtain a provirus, and to insert said virus into a suitable plasmid.
  • Another way is to isolate virion RNA or mRNA from SBL-6669 infected cells, form double stranded cDNA from said RNA and insert said double stranded cDNA into a phage lambda to form a recombinant DNA molecule, removing cDNA from said molecules and inserting cDNA into a suitable plasmid.
  • the resulting plasmid is transfected into a suitable bacteria, such as E. coli, fungi or cells.
  • Still another method to produce SBL-6669 antigens is to synthesize synthetic peptides where the amino acid sequence has been deduced from the primary nucleotide sequence of SBL-6669.
  • SBL-6669 virus or antigens prepared in any of the ways mentioned above can be used for several purposes as will be shown below.
  • a semi-purified SBL-6669 antigen (see Examples 2 and 3) is bound to an inert support, preferably polystyrene microtiter plates. The plates can be stored for several months. The sample to be tested, for instance serum, is then added. Antibodies specifically directed against SBL-6669 antigen are bound and can be detected by the addition of a labelled antihuman Ig G antibody.
  • a competitive ELISA can be performed where the SBL-6669 antigen is bound to the inert support via antibodies specifically directed against SBL-6669.
  • the sample to be tested is added together with labelled antibodies known to specifically bind to SBL-6669, and test serum competes with the labelled antibodies for the binding sites of the immobilized antigen.
  • a semi-purified SBL-6669 is. prepared in the same way as the antigen used in the ELISA (see Example 2).
  • the viral proteins are subjected to acrylamide electrophoresis and then transferred electrophoretically to nitrocellulose which is cut into strips.
  • By incubating the strips with samples to be tested antibodies directed against SBL-6669 are bound to the strips.
  • the bound antibodies are then visualized (see Example 4).
  • RIPA viral proteins are labelled by a radioisotope. Either lysed labelled virus infected cells of labelled virions can be used. We have found that best results are obtained by labelling U937 clone 16 cells at the peak of infection and preparing a cell lysate. At the peak of infection almost no production of cellular proteins occurs and hence a fairly pure antigen is obtained although a cell lysate is used.
  • the labelled antigen is incubated with. the sample to be tested and the formed immuno complexes bound to Protein A Sepharose. After washing the immuno complexes are dissolved and the remaining viral antigens are separated by SDS-polyacrylamide electrophoresis whereafter the labelled viral antigens are detected by autoradiography (see Example 5).
  • antigen was prepared by radiolabelling of persistently infected HUT 78 cells. This was done to allow comparison with HTLV-IV which we were only able to grow in HUT 78 cells.
  • the virion produced from the HUT 78 cells were lysed and used as RIPA antigen. However, it is more convenient to use a cell lysate in serodiagnosis.
  • To prepare the radiolabelled cell lysate labelling is performed as described in Example 5, however, in this case the radiolabelled cells are collected by centrifugation, washed three times in PBS and lysed in RIPA buffer. The cell lysate is clarified by centrifugation at 15 000 g for 15 minutes.
  • a future vaccine against AIDS will probably have to include not only HIV antigens but also HIV related human retrovirus antigens since there is limited if any cross-reaction between the envelope proteins of the two virus groups.
  • the present invention provides SBL-6669 antigens which may prove useful for active immunisation. Since a vaccine for maximum safety should be completely free from virus nucleic acid the strategy will be to use purified virus components, polypeptides expressed in bacteria, fungi or cells transformed with a recombinant vector containing cDNA from SBL-6669 or to use a synthetic SBL-6669 derived polypeptide.
  • SBL-6669 antigens prepared in any of the described ways in an animal an immune response is evoked.
  • Antibodies are produced against a variety of epitopes of the different viral proteins and polyclonal anti-SBL-6669 sera are obtained.
  • Monoclonal antibodies against SBL-6669 can be produced by fusing antibody synthesizing cells from the immunized animal with a suitable cell line by subsequent cloning and identification of antibody secreting clones. These monoclonal and polyclonal antibodies can be used in a variety of ways. One is bonding SBL-6669 antigen to the inert support of the competitive ELISA. Another is to detect SBL-6669 virus or antigens in samples such as body fluids.
  • such an antigen capture test comprises a solid phase where antibodies, human, polyclonal animal or monoclonal are bound to an inert support.
  • the test material is added in a liquid phase and viral antigens, if present, are captured by the antibodies of the solid phase.
  • Bound antigen is detected by the addition of antibodies against the antigen, these antibodies are either directly labelled or detected by a second labelled antibody.
  • Fig. 1 is an electron micrography showing the virus SBL-6669 (14 000 ⁇ 7.1).
  • Fig. 2 shows a cross characterisation of SBL-6669, HTLV-IV, LAV-II and HTLV-IIIB by RIPA. The method used is described in Example 5.
  • Figs. 3a and 3b show a cross characterisation of SBL-6669, HTLV-IV, LAV-II and HTLV-IIIB by Western blotting. The method used in described in Example 4.
  • the proviral DNA was obtained from a genomic library constructed from DNA of HUT-78 cells infected with SBL-6669-85 virus using the lambda-phage vector EMBL-3.
  • the uppermost row on each page and every fourth row of capitals therebelow discloses the nucleotide base sequence with the capitals A, C, G and T resp.
  • Virus SBL-6669 was isolated from peripheral blood mononuclear cells (PBMC) from a West African woman with clinical and immunological signs of immuno-deficiency although not fulfilling the criteria for AIDS.
  • PBMC peripheral blood mononuclear cells
  • the PBMC from the patient was obtained from 30 ml of heparinised blood which was separated by Ficoll-Paque according to the manufacturers' recommendations. 5 ⁇ 10 6 PBMC was cocultured with 5 ⁇ 10 6
  • PBMC peripheral blood mononuclear cells
  • U937 clone 2 cells with SBL-6669 virus. Like the HUT 78 cells these U937 clone 2 cells are chronically infected, grow without T-cell growth factor and have produced virus for several months.
  • SBL-6669 is antigenically closely related to the HIV related human retroviruses LAV-II and HTLV-IV but more distantly related to HTLV-IIIB (see Figs. 2 and 3).
  • Antigen was prepared from SBL-6669 virus grown on CEM and HUT 78 cells. The cells were sedimented and the culture media were concentrated 5- to 10-fold by ultrafiltration in a hollow fibre cassette system (Minisette TM , Filtron Scandinavia HB) with filters excluding molecules up to 300 kD. The concentrate was clarified twice by centrifugation at 10 000 g for 15 minutes. The virions were then pelleted at 16 000 g for 16-18 h, suspended in STE-buffer (0.1 M NaCl, 0.01 M
  • Tris-HCl, pH 7.5, 0.001 M EDTA Tris-HCl, pH 7.5, 0.001 M EDTA
  • the virions were resuspended in 1 ml/STE-buffer with the addition of 0.25%
  • Enzyme linked immunosorbent assay for detection of antibodies against HTLV-IV and LAV antigen were performed according to the following protocol.
  • Microtiter plates (Nunc microtiter modules, code No. 4-64394) were coated with
  • the reaction was allowed to take place for 30 minutes at room temperature and then stopped by adding 50 ⁇ l of 3 M sodium hydroxide to each well. Absorbance was read at 405 nm with a Titretek multiscanner (Flow Laboratories). The cut off value was determined as three times the absorbance value of a negative standard serum. Values between two and three times the control serum were suggested as border line values.
  • HTLV-IIIB virions were obtained as a gift from Dr. R.C. Gallo (National Cancer Institute, Bethesda).
  • HTLV-IV, SBL-6669 and LAV-II antigens were prepared from infected HUT 78 cells.
  • Virus from clarified supernatant was concentrated by centrifugation at 13 000 rpm over night followed by centrifugation through 30% sucrose in a SW 28 rotor (Beckman) at 13 000 rpm over night.
  • the virus pellet was resuspended in STE buffer (0.1 M NaCl, 0.01 M Tris-HCl, pH 7.5, 0.001 M EDTA) and stored at -70°C.
  • the virus preparation was diluted in Laemmli sample buffer and boiled for 2 minutes.
  • the viral proteins were separated by SDS-polyacrylamide gel electrophoresis (12% gels) and were then electrophoretically (100 V for three hours) transferred onto nitrocellulose.
  • the nitrocellulose sheet was cut into strips and incubated with 5% dry milk in phosphate buffered saline (PBS) for 30 minutes. Each strip was incubated over night at +4°C with human serum diluted 1:100 in PBS-BSA-T (PBS containing 0.1% bovine serum albumin and 0.1% Tween).
  • Virus (HTLV-IV, SBL-6669, LAV-II and HTLV-IIIB) propagated in HUT 78 cells was radioactively labelled by incubation for 12-14 hours in medium containing 35 S-cystein (150 ⁇ Ci/ml). Clarified (10 000 g, 10 minutes) supernatants were centrifuged at 60 000 g for 75 minutes. The pellet was lysed in RIPA buffer (140 mM NaCl, 1 mM dithiotreitol, 10 mM Tris, pH 8.0, 0.035% phenyl-methyl-sulfonylfluoride and 0.5% NP 40).
  • RIPA buffer 140 mM NaCl, 1 mM dithiotreitol, 10 mM Tris, pH 8.0, 0.035% phenyl-methyl-sulfonylfluoride and 0.5% NP 40).
  • Immunoprecipitates were analysed by SDS-polyacrylamide gel electrophoresis on 12% gels with 2.25% stacking gel. Each serum was reacted with the following antigens: A: HTLV-IIIB, B: HTLV-IV, C: SBL-6669, D: LAV-II. C 14 labelled molecular weight markers

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PCT/SE1988/000218 1987-04-28 1988-04-28 Hiv related human retrovirus strain with cloned nucleotide sequence and applications thereof WO1988008449A1 (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0400245A1 (en) * 1989-05-31 1990-12-05 Institut Pasteur Proteins and glycoproteins of the HIV-2 EHO retrovirus antiobodies directed against them - application for the diagnosis
EP0887427A2 (en) * 1997-06-25 1998-12-30 Ortho-Clinical Diagnostics, Inc. Amplification and detection of hiv-1 and/or hiv-2
US7803524B2 (en) 1994-02-23 2010-09-28 Siemens Healthcare Diagnostics Products Gmbh Antigenic HIV gp41 chimeric polypeptides comprising the MVP5180/91 epitope SKGKLIS

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2072853T3 (es) * 1988-06-09 1995-08-01 Innogenetics Nv Retrovirus hiv-3 y su utilizacion.
US5223423A (en) * 1989-03-31 1993-06-29 United States Of America Characterization of replication competent human immunodeficiency type 2 proviral clone hiv-2sbl/isy

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0165120A1 (fr) * 1983-09-15 1985-12-18 Institut Pasteur Rétrovirus associé aux lymphadénopathies et adapté à des lignées continues de cellules lymphoblastoides B, capables de produire en continu ledit rétrovirus et procédé pour leur obtention
WO1986004423A1 (en) * 1985-01-15 1986-07-31 Institute Of Cancer Research Improvements relating to viral isolates and their use
WO1987002892A1 (en) * 1985-11-14 1987-05-21 President And Fellows Of Harvard College T-lymphotrophic virus
WO1987004459A1 (fr) * 1986-01-22 1987-07-30 Institut Pasteur Retrovirus du type hiv-2 susceptible de provoquer le sida, et ses constituants antigeniques et nucleiques
WO1987006258A1 (en) * 1986-04-07 1987-10-22 United States Of America, Represented By The Unite A cell line producing aids viral antigens without producing infectious virus particles
EP0250128A2 (en) * 1986-06-18 1987-12-23 American Registry of Pathology Novel virus isolated from patients with aids
EP0253701A1 (en) * 1986-06-23 1988-01-20 Institut Pasteur Variants of lav viruses, their dna- and protein components and their uses, particularly for diagnostic purposes and for the preparation of immunogenic compositions

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0165120A1 (fr) * 1983-09-15 1985-12-18 Institut Pasteur Rétrovirus associé aux lymphadénopathies et adapté à des lignées continues de cellules lymphoblastoides B, capables de produire en continu ledit rétrovirus et procédé pour leur obtention
WO1986004423A1 (en) * 1985-01-15 1986-07-31 Institute Of Cancer Research Improvements relating to viral isolates and their use
WO1987002892A1 (en) * 1985-11-14 1987-05-21 President And Fellows Of Harvard College T-lymphotrophic virus
WO1987004459A1 (fr) * 1986-01-22 1987-07-30 Institut Pasteur Retrovirus du type hiv-2 susceptible de provoquer le sida, et ses constituants antigeniques et nucleiques
WO1987006258A1 (en) * 1986-04-07 1987-10-22 United States Of America, Represented By The Unite A cell line producing aids viral antigens without producing infectious virus particles
EP0250128A2 (en) * 1986-06-18 1987-12-23 American Registry of Pathology Novel virus isolated from patients with aids
EP0253701A1 (en) * 1986-06-23 1988-01-20 Institut Pasteur Variants of lav viruses, their dna- and protein components and their uses, particularly for diagnostic purposes and for the preparation of immunogenic compositions

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
NATURE, Vol. 326, 9 April 1987, HARDY KORNFELD et al., "Cloning of HTLV-r and its relation to simian and human immunodeficiency viruses", p. 610-613. *
NATURE, Vol. 326, 9 April 1987, PETER NEWMARK, "Variations of AIDS Virus Relatives", p. 548. *
SCIENCE, Vol. 232, No. 4747, 1986, PHYLLIS J. KANKI, "New Human T-Lymphotropic Retrovirus Related to Simian T-Lymphotropic Virus Type III (STLV-IIIAGM)", p. 238-243. *
SCIENCE, Vol. 233, 18 July 1986, FRANCOIS CLAVEL, "Isolation of a New Human Retrovirus from West African Patients with AIDS", p. 343-346. *
SCIENCE, Vol. 236, No. 4800, 24 April 1987, J.L. MARX, "The AIDS Virus-Well Known But a Mystery", p. 390-392. *
SCIENCE, Vol. 236, No. 4818, 19 June 1987, "Probing the AIDS Virus and its Relatives", p. 1523-1524. *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0400245A1 (en) * 1989-05-31 1990-12-05 Institut Pasteur Proteins and glycoproteins of the HIV-2 EHO retrovirus antiobodies directed against them - application for the diagnosis
EP0682951A1 (en) * 1989-05-31 1995-11-22 Institut Pasteur Proteins and glycoproteins of the HIV-2 EHO retrovirus antibodies direced against them - application for the diagnosis
US7803524B2 (en) 1994-02-23 2010-09-28 Siemens Healthcare Diagnostics Products Gmbh Antigenic HIV gp41 chimeric polypeptides comprising the MVP5180/91 epitope SKGKLIS
EP0887427A2 (en) * 1997-06-25 1998-12-30 Ortho-Clinical Diagnostics, Inc. Amplification and detection of hiv-1 and/or hiv-2
EP0887427A3 (en) * 1997-06-25 2001-10-17 Ortho-Clinical Diagnostics, Inc. Amplification and detection of hiv-1 and/or hiv-2

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