Restriction of HIV-1 genotypes in breast milk does not account for the population transmission genetic bottleneck that occurs following transmission.
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.
Heath
Laura
L
Department of Microbiology, University of Washington, Seattle, Washington, United States of America.
Conway
Susan
S
Jones
Laura
L
Semrau
Katherine
K
Nakamura
Kyle
K
Walter
Jan
J
Decker
W Don
WD
Hong
Jason
J
Chen
Thomas
T
Heil
Marintha
M
Sinkala
Moses
M
Kankasa
Chipepo
C
Thea
Donald M
DM
Kuhn
Louise
L
Mullins
James I
JI
Aldrovandi
Grace M
GM
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
D019302:HIV Envelope Protein gp160