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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection
Journal of Experimental Medicine, Volume 206, No. 6, Year 2009
Notification
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Description
Identification of full-length transmitted HIV-1 genomes could be instrumental in HIV-1 pathogenesis, microbicide, and vaccine research by enabling the direct analysis of those viruses actually responsible for productive clinical infection. We show in 12 acutely infected subjects (9 clade B and 3 clade C) that complete HIV-1 genomes of transmitted/founder viruses can be inferred by single genome amplification and sequencing of plasma virion RNA. This allowed for the molecular cloning and biological analysis of transmitted/founder viruses and a comprehensive genome-wide assessment of the genetic imprint left on the evolving virus quasispecies by a composite of host selection pressures. Transmitted viruses encoded intact canonical genes ( gag-pol-vif-vpr-tat-rev-vpu-env-nef) and replicated efficiently in primary human CD4+ T lymphocytes but much less so in monocyte-derived macrophages. Transmitted viruses were CD4 and CCR5 tropic and demonstrated concealment of coreceptor binding surfaces of the envelope bridging sheet and variable loop 3. 2 mo after infection, transmitted/founder viruses in three subjects were nearly completely replaced by viruses differing at two to five highly selected genomic loci; by 12-20 mo, viruses exhibited concentrated mutations at 17-34 discrete locations. These findings reveal viral properties associated with mucosal HIV-1 transmission and a limited set of rapidly evolving adaptive mutations driven primarily, but not exclusively, by early cytotoxic T cell responses. © 2009 Salazar-Gonzalez et al.
Authors & Co-Authors
Salazar-González, Jesús Fidel
United States, Birmingham
The University of Alabama at Birmingham
Salazar, Maria G.
United States, Birmingham
The University of Alabama at Birmingham
Keele, Brandon F.
United States, Birmingham
The University of Alabama at Birmingham
Learn, Gerald H.
United States, Birmingham
The University of Alabama at Birmingham
Giorgi, Elena Edi
United States, Los Alamos
Los Alamos National Laboratory
United States, Amherst
University of Massachusetts Amherst
Li, Hui
United States, Birmingham
The University of Alabama at Birmingham
Decker, Julie M.
United States, Birmingham
The University of Alabama at Birmingham
Wang, Shuyi
United States, Birmingham
The University of Alabama at Birmingham
Baalwa, Joshua
United States, Birmingham
The University of Alabama at Birmingham
Kraus, Matthias H.
United States, Birmingham
The University of Alabama at Birmingham
Parrish, Nicholas F.
United States, Birmingham
The University of Alabama at Birmingham
Shaw, Katharina S.
United States, Birmingham
The University of Alabama at Birmingham
Guffey, M. B.
United States, Birmingham
The University of Alabama at Birmingham
Bar, Katharine J.
United States, Birmingham
The University of Alabama at Birmingham
Davis, Katie L.
United States, Birmingham
The University of Alabama at Birmingham
Ochsenbauer, Christina
United States, Birmingham
The University of Alabama at Birmingham
Kappes, John
United States, Birmingham
The University of Alabama at Birmingham
Saag, Michael S.
United States, Birmingham
The University of Alabama at Birmingham
Cohen, Myron S.
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Mulenga, Joseph
Zambia, Lusaka
Zambia-emory Hiv Research Project
Derdeyn, Cynthia A.
United States, Atlanta
Emory University
Allen, Susan A.
United States, Atlanta
Emory University
Hunter, Eric
United States, Atlanta
Emory University
Markowitz, Martin M.
United States, New York
Aaron Diamond Aids Research Center
United States, New York
Rockefeller University
Hraber, Peter T.
United States, Los Alamos
Los Alamos National Laboratory
Perelson, Alan S.
United States, Los Alamos
Los Alamos National Laboratory
Bhattacharya, Tanmoy
United States, Los Alamos
Los Alamos National Laboratory
United States, Santa fe
Santa fe Institute
Haynes, Barton F.
United States, Durham
Duke University Medical Center
Korber, Bette T.
United States, Los Alamos
Los Alamos National Laboratory
United States, Santa fe
Santa fe Institute
Hahn, Beatrice H.
United States, Birmingham
The University of Alabama at Birmingham
Shaw, George M.
United States, Birmingham
The University of Alabama at Birmingham
Statistics
Citations: 785
Authors: 31
Affiliations: 10
Identifiers
Doi:
10.1084/jem.20090378
ISSN:
00221007
e-ISSN:
15409538
Research Areas
Genetics And Genomics
Infectious Diseases