THE ENVELOPE GLYCOPROTEIN ECTODOMAINS DETERMINE THE EFFICIENCY OF CD4(-LYMPHOCYTE DEPLETION IN SIMIAN-HUMAN IMMUNODEFICIENCY VIRUS-INFECTEDMACAQUES() T)

CD4(+) T lymphocyte depletion in human immunodeficiency virus type 1 ( HIV-1)-infected humans underlies the development of acquired immune de ficiency syndrome. Using a model in which rhesus macaques were infecte d with chimeric simian-human immunodeficiency viruses (SHIVs), we show that both the level of viremia and the structure of the HIV-1 envelop e glycoprotein ectodomains individually contributed to the efficiency with which CD4(+) T lymphocytes were depleted. The envelope glycoprote ins of recombinant SHIVs that efficiently caused loss of CD4(+) T lymp hocytes exhibited increased chemokine receptor binding and membrane-fu sing capacity compared with those of less pathogenic viruses. These st udies identify the HIV-1 envelope glycoprotein ectodomains as determin ants of CD4(+) T lymphocyte loss in vivo and provide a foundation for studying pathogenic mechanisms.