title: The envelope glycoprotein ectodomains determine the efficiency of CD4+ T lymphocyte depletion in simian-human immunodeficiency virus-infected macaques.
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.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: G B
authors.initials: GB
authors.lastname: Karlsson
authors.forename: M
authors.initials: M
authors.lastname: Halloran
authors.forename: D
authors.initials: D
authors.lastname: Schenten
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: P
authors.initials: P
authors.lastname: Racz
authors.forename: K
authors.initials: K
authors.lastname: Tenner-Racz
authors.forename: J
authors.initials: J
authors.lastname: Manola
authors.forename: R
authors.initials: R
authors.lastname: Gelman
authors.forename: B
authors.initials: B
authors.lastname: Etemad-Moghadam
authors.forename: E
authors.initials: E
authors.lastname: Desjardins
authors.forename: R
authors.initials: R
authors.lastname: Wyatt
authors.forename: N P
authors.initials: NP
authors.lastname: Gerard
authors.forename: L
authors.initials: L
authors.lastname: Marcon
authors.forename: D
authors.initials: D
authors.lastname: Margolin
authors.forename: J
authors.initials: J
authors.lastname: Fanton
authors.forename: M K
authors.initials: MK
authors.lastname: Axthelm
authors.forename: N L
authors.initials: NL
authors.lastname: Letvin
authors.forename: J
authors.initials: J
authors.lastname: Sodroski
mesh_terms: 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
chemical_list: D000998:Antiviral Agents; D014759:Viral Envelope Proteins