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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Restriction of HIV-1 genotypes in breast milk does not account for the population transmission genetic bottleneck that occurs following transmission
PLoS ONE, Volume 5, No. 4, Article e10213, Year 2010
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Description
Background: Breast milk transmission of HIV-1 remains a major route of pediatric infection. Defining the characteristics of viral variants to which breastfeeding infants are exposed is important for understanding the genetic bottleneck that occurs in the majority of mother-to-child transmissions. The blood-milk epithelial barrier markedly restricts the quantity of HIV-1 in breast milk, even in the absence of antiretroviral drugs. The basis of this restriction and the genetic relationship between breast milk and blood variants are not well established. Methodology/Principal Findings: We compared 356 HIV-1 subtype C gp160 envelope (env) gene sequences from the plasma and breast milk of 13 breastfeeding women. A trend towards lower viral population diversity and divergence in breast milk was observed, potentially indicative of clonal expansion within the breast. No differences in potential N-linked glycosylation site numbers or in gp160 variable loop amino acid lengths were identified. Genetic compartmentalization was evident in only one out of six subjects in whom contemporaneously obtained samples were studied. However, in samples that were collected 10 or more days apart, six of seven subjects were classified as having compartmentalized viral populations, highlighting the necessity of contemporaneous sampling for genetic compartmentalization studies. We found evidence of CXCR4 co-receptor using viruses in breast milk and blood in nine out of the thirteen subjects, but no evidence of preferential localization of these variants in either tissue. Conclusions/Significance: Despite marked restriction of HIV-1 quantities in milk, our data indicate intermixing of virus between blood and breast milk. Thus, we found no evidence that a restriction in viral genotype diversity in breast milk accounts for the genetic bottleneck observed following transmission. In addition, our results highlight the rapidity of HIV-1 env evolution and the importance of sample timing in analyses of gene flow. © 2010 Heath et al.
Authors & Co-Authors
Heath, Laura M.
United States, Seattle
University of Washington
Conway, Susan
United States, Los Angeles
Children's Hospital Los Angeles
Jones, Laura
United States, Los Angeles
Children's Hospital Los Angeles
Semrau, Katherine E.A.
United States, Boston
School of Public Health
Nakamura, Kyle J.
United States, Los Angeles
Children's Hospital Los Angeles
United States, Los Angeles
Keck School of Medicine of Usc
Walter, Jan
United States, Los Angeles
Children's Hospital Los Angeles
Decker, William Don
United States, Los Angeles
Children's Hospital Los Angeles
Hong, Jason
United States, Los Angeles
Children's Hospital Los Angeles
Chen, Thomas
United States, Los Angeles
Children's Hospital Los Angeles
Heil, Marintha L.
United States, Birmingham
The University of Alabama at Birmingham
Sinkala, Moses M.
Zambia, Lusaka
Lusaka District Health Management Team
Kankasa, Chipepo
Zambia, Lusaka
University Teaching Hospital Lusaka
Thea, Donald M.
United States, Boston
School of Public Health
Kuhn, Louise
United States, New York
Columbia University
Mullins, James I.
United States, Seattle
University of Washington
Aldrovandi, Grace M.
United States, Los Angeles
Children's Hospital Los Angeles
Statistics
Citations: 38
Authors: 16
Affiliations: 8
Identifiers
Doi:
10.1371/journal.pone.0010213
e-ISSN:
19326203
Research Areas
Genetics And Genomics
Infectious Diseases
Maternal And Child Health
Study Design
Cross Sectional Study
Participants Gender
Female