Adaptation of HIV-1 to its human host

Louise V. Wain, Elizabeth Bailes, Frederic Bibollet-Ruche, Julie M. Decker, Brandon F. Keele, Fran Van Heuverswyn, Yingying Li, Jun Takehisa, Eitel Mpoudi Ngole, George M. Shaw, Martine Peeters, Beatrice H. Hahn, Paid M. Sharp, Paul Sharp

Research output: Contribution to journalArticlepeer-review

Abstract

Human immunodeficiency virus type I (HIV- I) originated from three independent cross-species transmissions of simian immunodeficiency virus (SlVcpzPtt) infecting chimpanzees (Pan troglodytes troglodytes) in west central Africa, giving rise to pandemic (group M) and non-pandemic (groups N and 0) clades of HIV-1. To identify host-specific adaptations in HIV- I we compared the inferred ancestral sequences of HIV- I groups M, N and 0 to 12 full length genome sequences of SlVcpzPtt and four of the outlying but closely related SlVcpzPt.y (from P. t. schwehi irthii). This analysis revealed a single site that was completely conserved among SlVcpzPtt strains but different (due to the sarne change) in all three groups of HIV-1. This site, Gag-30, lies within p 17, the ga-encoded matrix protein. It is Met in SlVcpzPtt, underwent a conservative replacement by Leu in one lineage of SlVcpzPts 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- I 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- I and identify the viral matrix protein as a modulator of viral fitness following transmission to the new human host.

Original languageEnglish
Pages (from-to)1853-1860
Number of pages8
JournalMolecular Biology and Evolution
Volume24
Issue number8
DOIs
Publication statusPublished - Aug 2007

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