title: Restriction of HIV-1 genotypes in breast milk does not account for the population transmission genetic bottleneck that occurs following transmission.
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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Laura
authors.initials: L
authors.lastname: Heath
authors.forename: Susan
authors.initials: S
authors.lastname: Conway
authors.forename: Laura
authors.initials: L
authors.lastname: Jones
authors.forename: Katherine
authors.initials: K
authors.lastname: Semrau
authors.forename: Kyle
authors.initials: K
authors.lastname: Nakamura
authors.forename: Jan
authors.initials: J
authors.lastname: Walter
authors.forename: W Don
authors.initials: WD
authors.lastname: Decker
authors.forename: Jason
authors.initials: J
authors.lastname: Hong
authors.forename: Thomas
authors.initials: T
authors.lastname: Chen
authors.forename: Marintha
authors.initials: M
authors.lastname: Heil
authors.forename: Moses
authors.initials: M
authors.lastname: Sinkala
authors.forename: Chipepo
authors.initials: C
authors.lastname: Kankasa
authors.forename: Donald M
authors.initials: DM
authors.lastname: Thea
authors.forename: Louise
authors.initials: L
authors.lastname: Kuhn
authors.forename: James I
authors.initials: JI
authors.lastname: Mullins
authors.forename: Grace M
authors.initials: GM
authors.lastname: Aldrovandi
mesh_terms: D001483:Base Sequence; D005260:Female; D015752:Genes, env / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D019302:HIV Envelope Protein gp160 / Q000235:genetics; D015658:HIV Infections / Q000635:transmission*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008895:Milk, Human / Q000821:virology*; D011247:Pregnancy
chemical_list: D019302:HIV Envelope Protein gp160