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

Gunilla B. Karlsson, Matilda Halloran, John Li, In Woo Park, Raul Gomila, Keith A. Reimann, Michael K. Axthelm, Susan A. Iliff, Norman L. Letvin, Joseph Sodroski

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    176 Scopus citations

    Abstract

    In vivo passage of a chimeric simian-human immunodeficiency virus (SHIV- 89.6) expressing the human immunodeficiency virus type I (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 lung 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 SIV(mac) 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.

    Original languageEnglish (US)
    Pages (from-to)4218-4225
    Number of pages8
    JournalJournal of virology
    Volume71
    Issue number6
    StatePublished - Jun 1 1997

    ASJC Scopus subject areas

    • Microbiology
    • Immunology
    • Insect Science
    • Virology

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    Karlsson, G. B., Halloran, M., Li, J., Park, I. W., Gomila, R., Reimann, K. A., Axthelm, M. K., Iliff, S. A., Letvin, N. L., & Sodroski, J. (1997). Characterization of molecularly cloned simian-human immunodeficiency viruses causing rapid CD4+ lymphocyte depletion in rhesus monkeys. Journal of virology, 71(6), 4218-4225.