The envelope glycoprotein ectodomains determine the efficiency of CD4+ T lymphocyte depletion in simian-human immunodeficiency virus-infected macaques.
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.
Karlsson
G B
GB
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Halloran
M
M
Schenten
D
D
Lee
J
J
Racz
P
P
Tenner-Racz
K
K
Manola
J
J
Gelman
R
R
Etemad-Moghadam
B
B
Desjardins
E
E
Wyatt
R
R
Gerard
N P
NP
Marcon
L
L
Margolin
D
D
Fanton
J
J
Axthelm
M K
MK
Letvin
N L
NL
Sodroski
J
J
D000818:Animals; D000998:Antiviral Agents / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002678:Chimera / Q000276:immunology; D015726:Giant Cells / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D008198:Lymph Nodes / Q000821:virology; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008253:Macaca mulatta; D009500:Neutralization Tests; D017434:Protein Structure, Tertiary; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
D000998:Antiviral Agents; D014759:Viral Envelope Proteins