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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection
Proceedings of the National Academy of Sciences of the United States of America, Volume 105, No. 21, Year 2008
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Description
The precise identification of the HIV-1 envelope glycoprotein (Env) responsible for productive clinical infection could be instrumental in elucidating the molecular basis of HIV-1 transmission and in designing effective vaccines. Here, we developed a mathematical model of random viral evolution and, together with phylogenetic tree construction, used it to analyze 3,449 complete env sequences derived by single genome amplification from 102 subjects with acute HIV-1 (clade B) infection. Viral env genes evolving from individual transmitted or founder viruses generally exhibited a Poisson distribution of mutations and star-like phylogeny, which coalesced to an inferred consensus sequence at or near the estimated time of virus transmission. Overall, 78 of 102 subjects had evidence of productive clinical infection by a single virus, and 24 others had evidence of productive clinical infection by a minimum of two to five viruses. Phenotypic analysis of transmitted or early founder Envs revealed a consistent pattern of CCR5 dependence, masking of coreceptor binding regions, and equivalent or modestly enhanced resistance to the fusion inhibitor T1249 and broadly neutralizing antibodies compared with Envs from chronically infected subjects. Low multiplicity infection and limited viral evolution preceding peak viremia suggest a finite window of potential vulnerability of HIV-1 to vaccine-elicited immune responses, although phenotypic properties of transmitted Envs pose a formidable defense. © 2008 by The National Academy of Sciences of the USA.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC2387184/bin/0802203105_index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC2387184/bin/0802203105_Supplemental_PDF.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC2387184/bin/0802203105_SD1.xls
https://efashare.b-cdn.net/share/pmc/articles/PMC2387184/bin/0802203105_SD2.xls
https://efashare.b-cdn.net/share/pmc/articles/PMC2387184/bin/0802203105_SD3.xls
https://efashare.b-cdn.net/share/pmc/articles/PMC2387184/bin/0802203105_SD4.xls
https://efashare.b-cdn.net/share/pmc/articles/PMC2387184/bin/0802203105_SD5.xls
https://efashare.b-cdn.net/share/pmc/articles/PMC2387184/bin/0802203105_SD6.xls
https://efashare.b-cdn.net/share/pmc/articles/PMC2387184/bin/0802203105_SD7.xls
Authors & Co-Authors
Keele, Brandon F.
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
Salazar-González, Jesús Fidel
United States, Birmingham
The University of Alabama at Birmingham
Decker, Julie M.
United States, Birmingham
The University of Alabama at Birmingham
Pham, Kimmy T.
United States, Birmingham
The University of Alabama at Birmingham
Salazar, Maria G.
United States, Birmingham
The University of Alabama at Birmingham
Sun, Chuanxi
United States, Birmingham
The University of Alabama at Birmingham
Grayson, Truman
United States, Birmingham
The University of Alabama at Birmingham
Wang, Shuyi
United States, Birmingham
The University of Alabama at Birmingham
Li, Hui
United States, Birmingham
The University of Alabama at Birmingham
Wei, Xiping
United States, Birmingham
The University of Alabama at Birmingham
Jiang, Chunlai
United States, Durham
Duke University Medical Center
Kirchherr, Jennifer L.
United States, Durham
Duke University Medical Center
Gao, Feng
United States, Durham
Duke University Medical Center
Anderson, Jeffrey A.
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Ping, Lihua
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Swanstrom, Ronald I.
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Tomaras, Georgia D.
United States, Durham
Duke University Medical Center
Blattner, William A.
United States, College Park
University of Maryland, College Park
Goepfert, Paul A.
United States, Birmingham
The University of Alabama at Birmingham
Kilby, J. Michael
United States, Birmingham
The University of Alabama at Birmingham
Saag, Michael S.
United States, Birmingham
The University of Alabama at Birmingham
Delwart, E. L.
United States, San Francisco
Ucsf School of Medicine
Busch, Michael P.
United States, San Francisco
Ucsf School of Medicine
Cohen, Myron S.
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Montefiori, David Charles
United States, Durham
Duke University Medical Center
Haynes, Barton F.
United States, Durham
Duke University Medical Center
Gaschen, Brian K.
United States, Los Alamos
Los Alamos National Laboratory
Athreya, Gayathri S.
United States, Los Alamos
Los Alamos National Laboratory
Lee, Ha Y.
United States, Rochester
University of Rochester
Wood, Natasha T.
South Africa, Cape Town
University of Cape Town
Seoighe, Cathal
South Africa, Cape Town
University of Cape Town
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
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: 1,901
Authors: 37
Affiliations: 10
Identifiers
Doi:
10.1073/pnas.0802203105
ISSN:
00278424
Research Areas
Infectious Diseases