Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Adaptation of HIV-1 to Its Human Host
Molecular Biology and Evolution, Volume 24, No. 8, Year 2007
Notification
URL copied to clipboard!
Description
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. © The Author 2007. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved.
Authors & Co-Authors
Wain, Louise V.
United Kingdom, Nottingham
University of Nottingham
Bailes, Elizabeth
United Kingdom, Nottingham
University of Nottingham
Bibollet-Ruche, Frédéric
United States, Birmingham
The University of Alabama at Birmingham
Decker, Julie M.
United States, Birmingham
The University of Alabama at Birmingham
Keele, Brandon F.
United States, Birmingham
The University of Alabama at Birmingham
van Heuverswyn, Fran
France, Montpellier
Université de Montpellier
Li, Yingying
United States, Birmingham
The University of Alabama at Birmingham
Takehisa, Jun
United States, Birmingham
The University of Alabama at Birmingham
Ngole, Eitel Mpoudi
Cameroon, Yaounde
Projet Prevention du Sida au Cameroun Presica
Shaw, George M.
United States, Birmingham
The University of Alabama at Birmingham
Peeters, Martine F.
France, Montpellier
Université de Montpellier
Hahn, Beatrice H.
United States, Birmingham
The University of Alabama at Birmingham
Sharp, Paul M.
United Kingdom, Nottingham
University of Nottingham
Statistics
Citations: 117
Authors: 13
Affiliations: 4
Identifiers
Doi:
10.1093/molbev/msm110
ISSN:
07374038
e-ISSN:
15371719
Research Areas
Infectious Diseases
Study Design
Cohort Study
Study Approach
Quantitative