The envelope glycoprotein ectodomains determine the efficiency of CD4+ T lymphocyte depletion in simian-human immunodeficiency virus-infected macaques

Gunilla B. Karlsson, Matilda Halloran, Dominik Schenten, Juliette Lee, Paul Racz, Klara Tenner-Racz, Judith Manola, Rebecca Gelman, Bijan Etemad-Moghadam, Elizabeth Desjardins, Richard Wyatt, Norma P. Gerard, Luisa Marcon, David Margolin, John Fanton, Michael K. Axthelm, Norman L. Letvin, Joseph Sodroski

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    Abstract

    CD4+ T lymphocyte depletion in human immunodeficiency virus type 1 (HIV-1)-infected humans underlies the development of acquired immune deficiency syndrome. Using a model in which rhesus macaques were infected with chimeric simian-human immunodeficiency viruses (SHIVs), we show that both the level of viremia and the structure of the HIV-1 envelope glycoprotein ectodomains individually contributed to the efficiency with which CD4+ T lymphocytes were depleted. The envelope glycoproteins of recombinant SHIVs that efficiently caused loss of CD4+ T lymphocytes exhibited increased chemokine receptor binding and membrane-fusing capacity compared with those of less pathogenic viruses. These studies identify the HIV-1 envelope glycoprotein ectodomains as determinants of CD4+ T lymphocyte loss in vivo and provide a foundation for studying pathogenic mechanisms.

    Original languageEnglish (US)
    Pages (from-to)1159-1171
    Number of pages13
    JournalJournal of Experimental Medicine
    Volume188
    Issue number6
    DOIs
    StatePublished - Sep 21 1998

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    Keywords

    • CD4 T lymphocyte depletion
    • Envelope glycoprotein
    • Pathogenesis
    • Rhesus macaques
    • Simian-human immunodeficiency virus

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

    Cite this

    Karlsson, G. B., Halloran, M., Schenten, D., Lee, J., Racz, P., Tenner-Racz, K., Manola, J., Gelman, R., Etemad-Moghadam, B., Desjardins, E., Wyatt, R., Gerard, N. P., Marcon, L., Margolin, D., Fanton, J., Axthelm, M. K., Letvin, N. L., & Sodroski, J. (1998). The envelope glycoprotein ectodomains determine the efficiency of CD4+ T lymphocyte depletion in simian-human immunodeficiency virus-infected macaques. Journal of Experimental Medicine, 188(6), 1159-1171. https://doi.org/10.1084/jem.188.6.1159