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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Intercompartmental recombination of HIV-1 contributes to env intrahost diversity and modulates viral tropism and sensitivity to entry inhibitors
Journal of Virology, Volume 85, No. 12, Year 2011
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Description
HIV-1 circulates within an infected host as a genetically heterogeneous viral population. Viral intrahost diversity is shaped by substitutional evolution and recombination. Although many studies have speculated that recombination could have a significant impact on viral phenotype, this has never been definitively demonstrated. We report here phylogenetic and subsequent phenotypic analyses of envelope genes obtained from HIV-1 populations present in different anatomical compartments. Assessment of env compartmentalization from immunologically discrete tissues was assessed utilizing a single genome amplification approach, minimizing in vitro-generated artifacts. Genetic compartmentalization of variants was frequently observed. In addition, multiple incidences of intercompartment recombination, presumably facilitated by low-level migration of virus or infected cells between different anatomic sites and coinfection of susceptible cells by genetically divergent strains, were identified. These analyses demonstrate that intercompartment recombination is a fundamental evolutionary mechanism that helps to shape HIV-1 env intrahost diversity in natural infection. Analysis of the phenotypic consequences of these recombination events showed that genetic compartmentalization often correlates with phenotypic compartmentalization and that intercompartment recombination results in phenotype modulation. This represents definitive proof that recombination can generate novel combinations of phenotypic traits which differ subtly from those of parental strains, an important phenomenon that may have an impact on antiviral therapy and contribute to HIV-1 persistence in vivo. © 2011, American Society for Microbiology. All Rights Reserved.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3126287/bin/supp_85_12_6024__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC3126287/bin/supp_85_12_6024__SupplementaryFigure1.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3126287/bin/supp_85_12_6024__SupplementaryFig2a.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3126287/bin/supp_85_12_6024__SupplementaryFig2b.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3126287/bin/supp_85_12_6024__SupplementaryFig2c.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3126287/bin/supp_85_12_6024__SupplementaryFig2d.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3126287/bin/supp_85_12_6024__SupplementaryFig2e.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3126287/bin/supp_85_12_6024__Legends.doc
Authors & Co-Authors
Brown, Richard J.P.
United Kingdom, Nottingham
University of Nottingham
Peters, Paul J.
United States, Worcester
University of Massachusetts Chan Medical School
Caron, Catherine
United States, Worcester
University of Massachusetts Chan Medical School
Gonzalez-Perez, Maria Paz
United States, Worcester
University of Massachusetts Chan Medical School
Stones, Leanne
United Kingdom, Nottingham
University of Nottingham
Ankghuambom, Chiambah
United Kingdom, Nottingham
University of Nottingham
Pondei, Kemebradikumo
United Kingdom, Nottingham
University of Nottingham
McClure, C. Patrick
United Kingdom, Nottingham
University of Nottingham
Alemnji, George A.
Cameroon, Yaounde
Université de Yaoundé I
Taylor, Stephen Charles
United Kingdom, Birmingham
Heartlands Hospital
Sharp, Paul M.
United Kingdom, Edinburgh
The University of Edinburgh
Clapham, Paul R.
United States, Worcester
University of Massachusetts Chan Medical School
Ball, Jonathan K.
United Kingdom, Nottingham
University of Nottingham
Statistics
Citations: 13
Authors: 13
Affiliations: 5
Identifiers
Doi:
10.1128/JVI.00131-11
ISSN:
0022538X
e-ISSN:
10985514
Research Areas
Genetics And Genomics
Infectious Diseases
Study Design
Cross Sectional Study