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8th International AIDS ConferenceAmsterdam, Netherlands — July 19-24, 1992 |
Int Conf AIDS 1992 Jul 19-24; 8:We60 (abstract no. WeA 1080)
Gao F, Yue L, White A, Pappas P, Barchue J, Hanson A, Sharp P, Shaw G, Hahn B; University of Alabama, Birmingham.
OBJECTIVES: Current understanding of the natural history and phylogeny of Human Immunodeficiency Virus Type 2 (HIV-2) derives from studies of culture-amplified viruses from urban populations experiencing epidemic spread of infection and disease. Since tissue culture is highly selective for viral strains with an in vitro growth advantage, we hypothesized that such isolates may represent only a subset of a much larger and genetically more diverse group of viruses.
METHODS: Blood samples from two HIV-2 seropositive, healthy Liberian agricultural workers (F0784, 2238) and a symptomatic urban dweller from Cote d'Ivoire (7312A) were processed for virus culture and PCR analysis. Peripheral blood mononuclear cells were cultured alone, in combination with normal donor lymphocytes and macrophages, and with immortalized T-cell lines. HIV-2 sequences were amplified directly from uncultured PBMC DNA using nested PCR. Evolutionary trees were constructed using the neighbor-joining method.
RESULTS: Using nested PCR, HIV-2 sequences were identified in all three individuals. Viral isolates, however, were obtained only from subject 7312A but not from subjects FO784 and 2238, despite several attempts. Sequence analysis of PCR derived pol, env, and LTR regions revealed an unexpected degree of genotypic variation, with up to 23% sequence differences in regions where most HIV-2 viruses differ by less than 10%. Subsequent phylogenetic analysis identified one virus (HIV-2FO784) to be significantly more closely related to simian immunodeficiency viruses infecting sooty mangabeys and rhesus macaques than to any virus of human derivation, a second virus (HIV-2(2238)) to be most closely related to the previously reported highly divergent HIV-2O205) strain, and a third virus (HIV-2(7312A)) to represent a likely intergenic recombinant. In addition, one subject (FO784) was found to harbor multiply-defective viral genomes that resulted from G to A hypermutation.
CONCLUSIONS: These results indicate that HIV-2 in man and SIV in mangabeys and captive macaques represent members of a single, genetically-diverse group of viruses which cannot be separated into distinct phylogenetic lineages according to species of origin. Although the evolutionary origins and transmission patterns of this virus group remain to be defined, there is mounting evidence that the sooty mangabey is a natural reservoir and that human infections may represent a zoonosis.
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