Understanding the basis of CD4+ T-cell depletion in macaques infected by a simian-human immunodeficiency virus

Bijan Etemad-Moghadam, Daniela Rhone, Tavis Steenbeke, Ying Sun, Judith Manola, Rebecca Gelman, John W. Fanton, Paul Racz, Klara Tenner-Racz, Michael K. Axthelm, Norman L. Letvin, Joseph Sodroski

    Research output: Contribution to journalArticlepeer-review

    15 Scopus citations

    Abstract

    The efficacy of candidate AIDS vaccines to mediate protection against viral infection and pathogenesis is evaluated, at a preclinical stage, in animal models. One model that is favored because the infecting virus is closely related to HIV-1 and because of the rapidity of pathogenic outcomes is the infection of Old World monkeys by simian-human immunodeficiency virus (SHIV) chimerae. We investigated the basis for the depletion of CD4+ T lymphocytes in a SHIV-macaque model. Molecularly cloned SHIVs, SHIV-89.6 and SHIV-KB9, differ in the ability to cause CD4+ T-cell loss at a given level of virus replication in monkeys. The envelope glycoproteins of the pathogenic SHIV-KB9 mediate membrane-fusion in cultured T lymphocytes more efficiently than the envelope glycoproteins of the non-pathogenic SHIV-89.6. The minimal envelope glycoprotein region that specifies this increase in membrane-fusing capacity was sufficient to convert SHIV-89.6 into a virus that causes profound CD4+ T-cell depletion in monkeys. Conversely, two single amino acid changes that decrease the membrane-fusing ability of the SHIV-KB9 envelope glycoproteins also attenuated the CD4+ T-cell destruction that accompanied a given level of virus replication in SHIV-infected monkeys. Thus, the ability of the HIV-1 envelope glycoproteins to fuse membranes, which has been implicated in the induction of viral cytopathic effects in vitro, contributes to the capacity of the pathogenic SHIV to deplete CD4+ T lymphocytes in vivo.

    Original languageEnglish (US)
    Pages (from-to)1934-1937
    Number of pages4
    JournalVaccine
    Volume20
    Issue number15
    DOIs
    StatePublished - May 6 2002

    Keywords

    • CD4 T-cell depletion
    • Membrane fusion
    • Simian-human immunodeficiency virus

    ASJC Scopus subject areas

    • Molecular Medicine
    • Immunology and Microbiology(all)
    • veterinary(all)
    • Public Health, Environmental and Occupational Health
    • Infectious Diseases

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