Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/26367
Title: Adaptation of HIV-1 to its human host.
Authors: Wain, LV
Bailes, E
Bibollet-Ruche, F
Decker, JM
Keele, BF
Van Heuverswyn F
Li, Y
Takehisa, J
Ngole, EM
Shaw, GM
Peeters, M
Hahn, BH
Sharp, PM
First Published: Aug-2007
Citation: MOL BIOL EVOL, 2007, 24 (8), pp. 1853-1860
Abstract: Human immunodeficiency virus type 1 (HIV-1) originated from three independent cross-species transmissions of simian immunodeficiency virus (SIVcpzPtt) infecting chimpanzees (Pan troglodytes troglodytes) in west central Africa, giving rise to pandemic (group M) and non-pandemic (groups N and O) clades of HIV-1. To identify host-specific adaptations in HIV-1 we compared the inferred ancestral sequences of HIV-1 groups M, N and O to 12 full length genome sequences of SIVcpzPtt and four of the outlying but closely related SIVcpzPts (from P. t. schweinfurthii). This analysis revealed a single site that was completely conserved among SIVcpzPtt strains but different (due to the same change) in all three groups of HIV-1. This site, Gag-30, lies within p17, the gag-encoded matrix protein. It is Met in SIVcpzPtt, underwent a conservative replacement by Leu in one lineage of SIVcpzPts but changed radically to Arg on all three lineages leading to HIV-1. During subsequent diversification this site has been conserved as a basic residue (Arg or Lys) in most lineages of HIV-1. Retrospective analysis revealed that Gag-30 had reverted to Met in a previous experiment in which HIV-1 was passaged through chimpanzees. To examine whether this substitution conferred a species specific growth advantage, we used site-directed mutagenesis to generate variants of these chimpanzee-adapted HIV-1 strains with Lys at Gag-30, and tested their replication in both human and chimpanzee CD4+ T lymphocytes. Remarkably, viruses encoding Met replicated to higher titers than viruses encoding Lys in chimpanzee T cells, but the opposite was found in human T cells. Taken together, these observations provide compelling evidence for host-specific adaptation during the emergence of HIV-1 and identify the viral matrix protein as a modulator of viral fitness following transmission to the new human host.
DOI Link: 10.1093/molbev/msm110
ISSN: 0737-4038
Links: http://hdl.handle.net/2381/26367
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Health Sciences

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