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J Virol. 1997 June; 71(6): 4218–4225.
PMCID: PMC191636

Characterization of molecularly cloned simian-human immunodeficiency viruses causing rapid CD4+ lymphocyte depletion in rhesus monkeys.


In vivo passage of a chimeric simian-human immunodeficiency virus (SHIV-89.6) expressing the human immunodeficiency virus type 1 (HIV-1) tat, rev, vpu, and env genes generated pathogenic viruses (SHIV-89.6P) inducing rapid CD4+ lymphocyte depletion and AIDS-like illness in rhesus monkeys (K. Reimann, J. T. Li, R. Veazey, M. Halloran, I.-W. Park, G. B. Karlsson, J. Sodroski, and N. L. Letvin, J. Virol. 70:6922-6928, 1996). To characterize the molecular changes responsible for this increase in virulence, infectious proviral clones of SHIV-89.6P isolates were derived. Viruses generated from some of these clones caused a rapid and profound decline of CD4+ lymphocytes in a high percentage of inoculated monkeys. Nucleotide changes potentially responsible for the increased virulence of SHIV-89.6P were limited to the env, tat, or long terminal repeat sequences, with most of the observed changes in env. Nucleotide changes in env altered 12 amino acids in the gp120 and gp41 exterior domains, and a 140-bp deletion in env resulted in the substitution of the carboxyl terminus of the SIVmac gp41 glycoprotein for that of the HIV-1 gp41 glycoprotein. The availability of pathogenic proviral clones should facilitate dissection of the molecular determinants of SHIV-89.6P virulence.

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Selected References

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  • Cheng-Mayer C, Quiroga M, Tung JW, Dina D, Levy JA. Viral determinants of human immunodeficiency virus type 1 T-cell or macrophage tropism, cytopathogenicity, and CD4 antigen modulation. J Virol. 1990 Sep;64(9):4390–4398. [PMC free article] [PubMed]
  • Collman R, Balliet JW, Gregory SA, Friedman H, Kolson DL, Nathanson N, Srinivasan A. An infectious molecular clone of an unusual macrophage-tropic and highly cytopathic strain of human immunodeficiency virus type 1. J Virol. 1992 Dec;66(12):7517–7521. [PMC free article] [PubMed]
  • Daar ES, Li XL, Moudgil T, Ho DD. High concentrations of recombinant soluble CD4 are required to neutralize primary human immunodeficiency virus type 1 isolates. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6574–6578. [PubMed]
  • Dunn CS, Beyer C, Kieny MP, Gloeckler L, Schmitt D, Gut JP, Kirn A, Aubertin AM. High viral load and CD4 lymphopenia in rhesus and cynomolgus macaques infected by a chimeric primate lentivirus constructed using the env, rev, tat, and vpu genes from HIV-1 Lai. Virology. 1996 Sep 15;223(2):351–361. [PubMed]
  • Igarashi T, Shibata R, Hasebe F, Ami Y, Shinohara K, Komatsu T, Stahl-Hennig C, Petry H, Hunsmann G, Kuwata T, et al. Persistent infection with SIVmac chimeric virus having tat, rev, vpu, env and nef of HIV type 1 in macaque monkeys. AIDS Res Hum Retroviruses. 1994 Aug;10(8):1021–1029. [PubMed]
  • Javaherian K, Langlois AJ, Schmidt S, Kaufmann M, Cates N, Langedijk JP, Meloen RH, Desrosiers RC, Burns DP, Bolognesi DP, et al. 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. [PubMed]
  • Joag SV, Li Z, Foresman L, Stephens EB, Zhao LJ, Adany I, Pinson DM, McClure HM, Narayan O. Chimeric simian/human immunodeficiency virus that causes progressive loss of CD4+ T cells and AIDS in pig-tailed macaques. J Virol. 1996 May;70(5):3189–3197. [PMC free article] [PubMed]
  • Lackner AA. Pathology of simian immunodeficiency virus induced disease. Curr Top Microbiol Immunol. 1994;188:35–64. [PubMed]
  • Letvin NL. Animal models for the study of human immunodeficiency virus infections. Curr Opin Immunol. 1992 Aug;4(4):481–485. [PubMed]
  • Li J, Lord CI, Haseltine W, Letvin NL, 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]
  • Li JT, Halloran M, Lord CI, Watson A, Ranchalis J, Fung M, Letvin NL, Sodroski JG. Persistent infection of macaques with simian-human immunodeficiency viruses. J Virol. 1995 Nov;69(11):7061–7067. [PMC free article] [PubMed]
  • Luciw PA, Pratt-Lowe E, Shaw KE, Levy JA, Cheng-Mayer C. Persistent infection of rhesus macaques with T-cell-line-tropic and macrophage-tropic clones of simian/human immunodeficiency viruses (SHIV). Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7490–7494. [PubMed]
  • Reimann KA, Waite BC, Lee-Parritz DE, Lin W, Uchanska-Ziegler B, O'Connell MJ, Letvin NL. Use of human leukocyte-specific monoclonal antibodies for clinically immunophenotyping lymphocytes of rhesus monkeys. Cytometry. 1994 Sep 1;17(1):102–108. [PubMed]
  • Reimann KA, Li JT, Veazey R, Halloran M, Park IW, Karlsson GB, Sodroski J, Letvin NL. A chimeric simian/human immunodeficiency virus expressing a primary patient human immunodeficiency virus type 1 isolate env causes an AIDS-like disease after in vivo passage in rhesus monkeys. J Virol. 1996 Oct;70(10):6922–6928. [PMC free article] [PubMed]
  • Reimann KA, Li JT, Voss G, Lekutis C, Tenner-Racz K, Racz P, Lin W, Montefiori DC, Lee-Parritz DE, Lu Y, et al. An env gene derived from a primary human immunodeficiency virus type 1 isolate confers high in vivo replicative capacity to a chimeric simian/human immunodeficiency virus in rhesus monkeys. J Virol. 1996 May;70(5):3198–3206. [PMC free article] [PubMed]
  • Sakuragi S, Shibata R, Mukai R, Komatsu T, Fukasawa M, Sakai H, Sakuragi J, Kawamura M, Ibuki K, Hayami M, et al. Infection of macaque monkeys with a chimeric human and simian immunodeficiency virus. J Gen Virol. 1992 Nov;73(Pt 11):2983–2987. [PubMed]
  • Shioda T, Levy JA, Cheng-Mayer C. Macrophage and T cell-line tropisms of HIV-1 are determined by specific regions of the envelope gp120 gene. Nature. 1991 Jan 10;349(6305):167–169. [PubMed]
  • Sullivan N, Sun Y, Li J, Hofmann W, Sodroski J. Replicative function and neutralization sensitivity of envelope glycoproteins from primary and T-cell line-passaged human immunodeficiency virus type 1 isolates. J Virol. 1995 Jul;69(7):4413–4422. [PMC free article] [PubMed]
  • Voss G, Li J, Manson K, Wyand M, Sodroski J, Letvin NL. Human immunodeficiency virus type 1 envelope glycoprotein-specific cytotoxic T lymphocytes in simian-human immunodeficiency virus-infected rhesus monkeys. Virology. 1995 Apr 20;208(2):770–775. [PubMed]

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