title: Derivation and characterization of a highly pathogenic isolate of human immunodeficiency virus type 2 that causes rapid CD4+ cell depletion in Macaca nemestrina.
abstract: With few exceptions, humans are the only species known to develop acquired immunodeficiency syndrome (AIDS) after human immunodeficiency virus (HIV) infection. We report here that an isolate of HIV type 2, EHO, readily established persistent infection in 100% of Macaca nemestrina in three consecutive transmission studies. Of the eight infected animals, five showed persistently high virus load and six developed AIDS-like diseases or CD4+ cell depletion within 4 years of infection. The pathology and clinical signs closely parallel those of HIV-1 infection of humans, including lymphadenopathy, anemia, CD4+ cell depletion, and opportunistic infections. A cell-free virus stock was established from the lymph nodes of an animal that developed AIDS-like diseases. This virus, HIV-2/287, was highly pathogenic in M. nemestrina, causing CD4+ cell depletion within 2-8 weeks postinfection. While both HIV-2 EHO and HIV-2/287 use predominantly CXCR4, the latter shows greatly enhanced replicative capacity in macaque peripheral blood mononuclear cells (PBMCs). The establishment of a human immunodeficiency virus that causes rapid and reproducible CD4 cell depletion in macaques could facilitate the study of HIV pathogenesis and the development of effective vaccines and therapy against AIDS.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121, USA.
authors.forename: J
authors.initials: J
authors.lastname: McClure
authors.forename: A M
authors.initials: AM
authors.lastname: Schmidt
authors.forename: M A
authors.initials: MA
authors.lastname: Rey-Cuille
authors.forename: J
authors.initials: J
authors.lastname: Bannink
authors.forename: L
authors.initials: L
authors.lastname: Misher
authors.forename: C C
authors.initials: CC
authors.lastname: Tsai
authors.forename: D M
authors.initials: DM
authors.lastname: Anderson
authors.forename: W R
authors.initials: WR
authors.lastname: Morton
authors.forename: S L
authors.initials: SL
authors.lastname: Hu
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology; D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D004195:Disease Models, Animal; D015483:HIV Antibodies / Q000097:blood; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000472:pathogenicity; D015498:HIV-2 / Q000302:isolation & purification / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology / Q000821:virology; D008254:Macaca nemestrina; D016133:Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000502:physiology; D014771:Virion / Q000302:isolation & purification; D014779:Virus Replication
chemical_list: D015483:HIV Antibodies; D019718:Receptors, CXCR4