TY - JOUR
T1 - The envelope glycoprotein ectodomains determine the efficiency of CD4+ T lymphocyte depletion in simian-human immunodeficiency virus-infected macaques
AU - Karlsson, Gunilla B.
AU - Halloran, Matilda
AU - Schenten, Dominik
AU - Lee, Juliette
AU - Racz, Paul
AU - Tenner-Racz, Klara
AU - Manola, Judith
AU - Gelman, Rebecca
AU - Etemad-Moghadam, Bijan
AU - Desjardins, Elizabeth
AU - Wyatt, Richard
AU - Gerard, Norma P.
AU - Marcon, Luisa
AU - Margolin, David
AU - Fanton, John
AU - Axthelm, Michael K.
AU - Letvin, Norman L.
AU - Sodroski, Joseph
PY - 1998/9/21
Y1 - 1998/9/21
N2 - 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.
AB - 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.
KW - CD4 T lymphocyte depletion
KW - Envelope glycoprotein
KW - Pathogenesis
KW - Rhesus macaques
KW - Simian-human immunodeficiency virus
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U2 - 10.1084/jem.188.6.1159
DO - 10.1084/jem.188.6.1159
M3 - Article
C2 - 9743534
AN - SCOPUS:0032555938
SN - 0022-1007
VL - 188
SP - 1159
EP - 1171
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 6
ER -