Restriction of HIV-1 Genotypes in Breast Milk Does Not Account for the Population Transmission Genetic Bottleneck That Occurs following Transmission


Show simple item record Heath, Laura en_US Conway, Susan en_US Jones, Laura en_US Semrau, Katherine en_US Nakamura, Kyle en_US Walter, Jan en_US Decker, W. Don en_US Hong, Jason en_US Chen, Thomas en_US Heil, Marintha en_US Sinkala, Moses en_US Kankasa, Chipepo en_US Thea, Donald M. en_US Kuhn, Louise en_US Mullins, James I. en_US Aldrovandi, Grace M. en_US 2012-01-11T21:44:36Z 2012-01-11T21:44:36Z 2010-4-20 en_US
dc.identifier.citation Heath, Laura, Susan Conway, Laura Jones, Katherine Semrau, Kyle Nakamura, Jan Walter, W. Don Decker, Jason Hong, Thomas Chen, Marintha Heil, Moses Sinkala, Chipepo Kankasa, Donald M. Thea, Louise Kuhn, James I. Mullins, Grace M. Aldrovandi. "Restriction of HIV-1 Genotypes in Breast Milk Does Not Account for the Population Transmission Genetic Bottleneck That Occurs following Transmission" PLoS ONE 5(4): e10213. (2010) en_US
dc.identifier.issn 1932-6203 en_US
dc.description.abstract 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. en_US
dc.description.sponsorship National Institute of Child Health and Human Development; National Institutes of Health (R01 HD 39611, R01 HD 40777); International Maternal Pediatric Adolescent AIDS Clinical Trials Group (U01 AI068632-01); National Institutes of Health Cellular, Biochemical; Molecular Sciences Training Program Grant (T 32 067587) en_US
dc.language.iso en en_US
dc.publisher Public Library of Science en_US
dc.rights Heath et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. en_US
dc.title Restriction of HIV-1 Genotypes in Breast Milk Does Not Account for the Population Transmission Genetic Bottleneck That Occurs following Transmission en_US
dc.type article en_US
dc.identifier.doi 10.1371/journal.pone.0010213 en_US
dc.identifier.pubmedid 20422033 en_US
dc.identifier.pmcid 2857876 en_US

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