Derivation and characterization of a highly pathogenic isolate of human immunodeficiency virus type 2 that causes rapid CD4(+) cell depletion in Macaca nemestrina

With few exceptions, humans are the only species known to develop acquired immunodeficiency syndrome (AIDS) after human immunodeficiency virus (HIV) i nfection. We report here that an isolate of HIV type 2, EHO, readily establ ished persistent infection in 100% of Macaca nemestrina in three consecutiv e transmission studies. Of the eight infected animals, five showed persiste ntly high virus load and six developed AIDS-like diseases or CD4(+) cell de pletion within 4 years of infection. The pathology and clinical signs close ly parallel those of HIV-1 infection of humans, including lymphadenopathy, anemia, CD4(+) cell depletion, and opportunistic infections. A cell-free vi rus 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. neme strina, causing CD4(+) cell depletion within 2-8 weeks postinfection. While both HIV-2 EHO and HIV-2/287 use predominantly CXCR4, the latter shows gre atly enhanced replicative capacity in macaque peripheral blood mononuclear cells (PBMCs). The establishment of a human immunodeficiency virus that cau ses rapid and reproducible CD4(+) cell depletion in macaques could facilita te the study of HIV pathogenesis and the development of effective vaccines and therapy against AIDS.