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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Origin and evolution of HIV-1 in breast milk determined by single-genome amplification and sequencing
Journal of Virology, Volume 85, No. 6, Year 2011
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Description
HIV transmission via breastfeeding accounts for a considerable proportion of infant HIV acquisition. However, the origin and evolution of the virus population in breast milk, the likely reservoir of transmitted virus variants, are not well characterized. In this study, HIV envelope (env) genes were sequenced from virus variants amplified by single-genome amplification from plasmas and milk of 12 chronically HIV-infected, lactating Malawian women. Maximum likelihood trees and statistical tests of compartmentalization revealed interspersion of plasma and milk HIV env sequences in the majority of subjects, indicating limited or no compartmentalization of milk virus variants. However, phylogenetic tree analysis further revealed monotypic virus variants that were significantly more frequent in milk (median proportion of identical viruses, 29.5%; range, 0 to 61%) than in plasma (median proportion of identical viruses, 0%; range, 0 to 26%) (P = 0.002), suggesting local virus replication in the breast milk compartment. Moreover, clonally amplified virus env genes in milk produced functional virus Envs that were all CCR5 tropic. Milk and plasma virus Envs had similar predicted phenotypes and neutralization sensitivities to broadly neutralizing antibodies in both transmitting and nontransmitting mothers. Finally, phylogenetic comparison of longitudinal milk and plasma virus env sequences revealed synchronous virus evolution and new clonal amplification of evolved virus env genes in milk. The limited compartmentalization and the clonal amplification of evolving, functional viruses in milk indicate continual seeding of the mammary gland by blood virus variants, followed by transient local replication of these variants in the breast milk compartment. Copyright © 2011, American Society for Microbiology. All Rights Reserved.
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
Learn, Gerald H.
United States, Birmingham
The University of Alabama at Birmingham
Fouda, Genevieve G.A.
United States, Durham
Duke University School of Medicine
Kang, Helen H.
United States, Boston
Harvard Medical School
Mahlokozera, Tatenda
United States, Boston
Harvard Medical School
Wilks, Andrew B.
United States, Boston
Harvard Medical School
Lovingood, Rachel V.
United States, Durham
Duke University School of Medicine
Stacey, Andrea R.
United Kingdom, Oxford
Nuffield Department of Medicine
Kalilani-Phiri, Linda V.
Malawi, Zomba
University of Malawi
Meshnick, Steven Richard
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Borrow, Persephone
United Kingdom, Oxford
Nuffield Department of Medicine
Montefiori, David Charles
United States, Durham
Duke University School of Medicine
Denny, Thomas N.
United States, Durham
Duke University School of Medicine
Letvin, Norman L.
United States, Boston
Harvard Medical School
Shaw, George M.
United States, Birmingham
The University of Alabama at Birmingham
Hahn, Beatrice H.
United States, Birmingham
The University of Alabama at Birmingham
Permar, Sallie Robey
United States, Boston
Harvard Medical School
United States, Boston
Boston Children's Hospital
Statistics
Citations: 67
Authors: 18
Affiliations: 7
Identifiers
Doi:
10.1128/JVI.02316-10
ISSN:
0022538X
e-ISSN:
10985514
Research Areas
Infectious Diseases
Maternal And Child Health
Study Design
Cross Sectional Study
Cohort Study
Participants Gender
Female