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. 1995 Oct;69(10):6424–6429. doi: 10.1128/jvi.69.10.6424-6429.1995

An infectious chimeric human immunodeficiency virus type 2 (HIV-2) expressing the HIV-1 principal neutralizing determinant.

M Mamounas 1, D J Looney 1, R Talbott 1, F Wong-Staal 1
PMCID: PMC189542  PMID: 7666543

Abstract

The human immunodeficiency virus type 1 strain MN (HIV-1MN) principal neutralizing determinant (PND, V3 loop) was introduced into infectious molecular clones HIV-2KR and simian immunodeficiency virus mm239 (SIVmm239) by hybridization PCR, replacing the corresponding HIV-2 or SIV envelope cysteine loops with the HIV-1 coding sequence. The HIV-2 chimera (HIV-2KR-MNV3) was found to be capable of infecting a number of T-cell lymphoblastic cell lines as well as primary peripheral blood mononuclear cells. In contrast, the SIV chimera (SIV239MNV3) was not replication competent. Envelope produced by HIV-2KR-MNV3 but not the parental HIV-2KR was recognized by V3-specific and HIV-1-specific polyclonal antisera in radioimmunoprecipitation assays. HIV-2-specific antisera recognized both the chimeric and parental virus but not HIV-1MN. The chimeric HIV-2KR-MNV3 virus proved to be exquisitely susceptible to neutralization by HIV-1-specific and V3-specific antisera, suggesting the potential for use in animal models designed to test HIV-1 vaccine candidates which target the PND.

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Selected References

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  1. Agy M. B., Frumkin L. R., Corey L., Coombs R. W., Wolinsky S. M., Koehler J., Morton W. R., Katze M. G. Infection of Macaca nemestrina by human immunodeficiency virus type-1. Science. 1992 Jul 3;257(5066):103–106. doi: 10.1126/science.1621083. [DOI] [PubMed] [Google Scholar]
  2. Arthur L. O., Bess J. W., Jr, Waters D. J., Pyle S. W., Kelliher J. C., Nara P. L., Krohn K., Robey W. G., Langlois A. J., Gallo R. C. Challenge of chimpanzees (Pan troglodytes) immunized with human immunodeficiency virus envelope glycoprotein gp120. J Virol. 1989 Dec;63(12):5046–5053. doi: 10.1128/jvi.63.12.5046-5053.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barnett S. W., Quiroga M., Werner A., Dina D., Levy J. A. Distinguishing features of an infectious molecular clone of the highly divergent and noncytopathic human immunodeficiency virus type 2 UC1 strain. J Virol. 1993 Feb;67(2):1006–1014. doi: 10.1128/jvi.67.2.1006-1014.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Björling E., Chiodi F., Utter G., Norrby E. Two neutralizing domains in the V3 region in the envelope glycoprotein gp125 of HIV type 2. J Immunol. 1994 Feb 15;152(4):1952–1959. [PubMed] [Google Scholar]
  5. Castro B. A., Nepomuceno M., Lerche N. W., Eichberg J. W., Levy J. A. Persistent infection of baboons and rhesus monkeys with different strains of HIV-2. Virology. 1991 Sep;184(1):219–226. doi: 10.1016/0042-6822(91)90838-3. [DOI] [PubMed] [Google Scholar]
  6. Emini E. A., Schleif W. A., Nunberg J. H., Conley A. J., Eda Y., Tokiyoshi S., Putney S. D., Matsushita S., Cobb K. E., Jett C. M. Prevention of HIV-1 infection in chimpanzees by gp120 V3 domain-specific monoclonal antibody. Nature. 1992 Feb 20;355(6362):728–730. doi: 10.1038/355728a0. [DOI] [PubMed] [Google Scholar]
  7. Franchini G., Markham P., Gard E., Fargnoli K., Keubaruwa S., Jagodzinski L., Robert-Guroff M., Lusso P., Ford G., Wong-Staal F. Persistent infection of rhesus macaques with a molecular clone of human immunodeficiency virus type 2: evidence of minimal genetic drift and low pathogenetic effects. J Virol. 1990 Sep;64(9):4462–4467. doi: 10.1128/jvi.64.9.4462-4467.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Frumkin L. R., Agy M. B., Coombs R. W., Panther L., Morton W. R., Koehler J., Florey M. J., Dragavon J., Schmidt A., Katze M. G. Acute infection of Macaca nemestrina by human immunodeficiency virus type 1. Virology. 1993 Aug;195(2):422–431. doi: 10.1006/viro.1993.1392. [DOI] [PubMed] [Google Scholar]
  9. Fultz P. N. Nonhuman primate models for AIDS. Clin Infect Dis. 1993 Aug;17 (Suppl 1):S230–S235. doi: 10.1093/clinids/17.supplement_1.s230. [DOI] [PubMed] [Google Scholar]
  10. Gorny M. K., Conley A. J., Karwowska S., Buchbinder A., Xu J. Y., Emini E. A., Koenig S., Zolla-Pazner S. Neutralization of diverse human immunodeficiency virus type 1 variants by an anti-V3 human monoclonal antibody. J Virol. 1992 Dec;66(12):7538–7542. doi: 10.1128/jvi.66.12.7538-7542.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hirsch V. M., Martin J. E., Dapolito G., Elkins W. R., London W. T., Goldstein S., Johnson P. R. Spontaneous substitutions in the vicinity of the V3 analog affect cell tropism and pathogenicity of simian immunodeficiency virus. J Virol. 1994 Apr;68(4):2649–2661. doi: 10.1128/jvi.68.4.2649-2661.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hwang S. S., Boyle T. J., Lyerly H. K., Cullen B. R. Identification of the envelope V3 loop as the primary determinant of cell tropism in HIV-1. Science. 1991 Jul 5;253(5015):71–74. doi: 10.1126/science.1905842. [DOI] [PubMed] [Google Scholar]
  13. Javaherian K., Langlois A. J., Schmidt S., Kaufmann M., Cates N., Langedijk J. P., Meloen R. H., Desrosiers R. C., Burns D. P., Bolognesi D. P. The principal neutralization determinant of simian immunodeficiency virus differs from that of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1418–1422. doi: 10.1073/pnas.89.4.1418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kirchhoff F., Mori K., Desrosiers R. C. The "V3" domain is a determinant of simian immunodeficiency virus cell tropism. J Virol. 1994 Jun;68(6):3682–3692. doi: 10.1128/jvi.68.6.3682-3692.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kirchhoff F., Morrison H. G., Murray M. G., Rennert P., Desrosiers R. C. SIVmac expressing hybrid envelope proteins containing HIV-1 V3 and/or C4 sequences is not competent for replication. AIDS Res Hum Retroviruses. 1994 Mar;10(3):309–313. doi: 10.1089/aid.1994.10.309. [DOI] [PubMed] [Google Scholar]
  16. Koch J. A., Ruprecht R. M. Animal models for anti-AIDS therapy. Antiviral Res. 1992 Aug;19(2):81–109. doi: 10.1016/0166-3542(92)90069-h. [DOI] [PubMed] [Google Scholar]
  17. Letvin N. L. Nonhuman primate models for HIV vaccine development. Immunodefic Rev. 1992;3(3):247–260. [PubMed] [Google Scholar]
  18. Li J., Lord C. I., Haseltine W., Letvin N. L., Sodroski J. Infection of cynomolgus monkeys with a chimeric HIV-1/SIVmac virus that expresses the HIV-1 envelope glycoproteins. J Acquir Immune Defic Syndr. 1992;5(7):639–646. [PubMed] [Google Scholar]
  19. Lusso P., Markham P. D., Ranki A., Earl P., Moss B., Dorner F., Gallo R. C., Krohn K. J. Cell-mediated immune response toward viral envelope and core antigens in gibbon apes (Hylobates lar) chronically infected with human immunodeficiency virus-1. J Immunol. 1988 Oct 1;141(7):2467–2473. [PubMed] [Google Scholar]
  20. Otten R. A., Brown B. G., Simon M., Lupo L. D., Parekh B. S., Lairmore M. D., Schable C. A., Schochetman G., Rayfield M. A. Differential replication and pathogenic effects of HIV-1 and HIV-2 in Macaca nemestrina. AIDS. 1994 Mar;8(3):297–306. doi: 10.1097/00002030-199403000-00002. [DOI] [PubMed] [Google Scholar]
  21. Palker T. J., Clark M. E., Langlois A. J., Matthews T. J., Weinhold K. J., Randall R. R., Bolognesi D. P., Haynes B. F. Type-specific neutralization of the human immunodeficiency virus with antibodies to env-encoded synthetic peptides. Proc Natl Acad Sci U S A. 1988 Mar;85(6):1932–1936. doi: 10.1073/pnas.85.6.1932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Palker T. J., Matthews T. J., Langlois A., Tanner M. E., Martin M. E., Scearce R. M., Kim J. E., Berzofsky J. A., Bolognesi D. P., Haynes B. F. Polyvalent human immunodeficiency virus synthetic immunogen comprised of envelope gp120 T helper cell sites and B cell neutralization epitopes. J Immunol. 1989 May 15;142(10):3612–3619. [PubMed] [Google Scholar]
  23. Putkonen P., Thorstensson R., Albert J., Hild K., Norrby E., Biberfeld P., Biberfeld G. Infection of cynomolgus monkeys with HIV-2 protects against pathogenic consequences of a subsequent simian immunodeficiency virus infection. AIDS. 1990 Aug;4(8):783–789. doi: 10.1097/00002030-199008000-00010. [DOI] [PubMed] [Google Scholar]
  24. Regier D. A., Desrosiers R. C. The complete nucleotide sequence of a pathogenic molecular clone of simian immunodeficiency virus. AIDS Res Hum Retroviruses. 1990 Nov;6(11):1221–1231. doi: 10.1089/aid.1990.6.1221. [DOI] [PubMed] [Google Scholar]
  25. Robert-Guroff M., Louie A., Myagkikh M., Michaels F., Kieny M. P., White-Scharf M. E., Potts B., Grogg D., Reitz M. S., Jr Alteration of V3 loop context within the envelope of human immunodeficiency virus type 1 enhances neutralization. J Virol. 1994 Jun;68(6):3459–3466. doi: 10.1128/jvi.68.6.3459-3466.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Shioda T., Levy J. A., Cheng-Mayer C. Small amino acid changes in the V3 hypervariable region of gp120 can affect the T-cell-line and macrophage tropism of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9434–9438. doi: 10.1073/pnas.89.20.9434. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Smith A. D., Resnick D. A., Zhang A., Geisler S. C., Arnold E., Arnold G. F. Use of random systematic mutagenesis to generate viable human rhinovirus 14 chimeras displaying human immunodeficiency virus type 1 V3 loop sequences. J Virol. 1994 Jan;68(1):575–579. doi: 10.1128/jvi.68.1.575-579.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Talbott R., Kraus G., Looney D., Wong-Staal F. Mapping the determinants of human immunodeficiency virus 2 for infectivity, replication efficiency, and cytopathicity. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4226–4230. doi: 10.1073/pnas.90.9.4226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wang C. Y., Looney D. J., Li M. L., Walfield A. M., Ye J., Hosein B., Tam J. P., Wong-Staal F. Long-term high-titer neutralizing activity induced by octameric synthetic HIV-1 antigen. Science. 1991 Oct 11;254(5029):285–288. doi: 10.1126/science.254.5029.285. [DOI] [PubMed] [Google Scholar]
  30. Watkins B. A., Davis A. E., Cocchi F., Reitz M. S., Jr A rapid method for site-specific mutagenesis using larger plasmids as templates. Biotechniques. 1993 Oct;15(4):700–704. [PubMed] [Google Scholar]
  31. Westervelt P., Gendelman H. E., Ratner L. Identification of a determinant within the human immunodeficiency virus 1 surface envelope glycoprotein critical for productive infection of primary monocytes. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3097–3101. doi: 10.1073/pnas.88.8.3097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. White-Scharf M. E., Potts B. J., Smith L. M., Sokolowski K. A., Rusche J. R., Silver S. Broadly neutralizing monoclonal antibodies to the V3 region of HIV-1 can be elicited by peptide immunization. Virology. 1993 Jan;192(1):197–206. doi: 10.1006/viro.1993.1022. [DOI] [PubMed] [Google Scholar]

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