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Journal of virology
Oct, 2010;84 (20): 10812-9.

Genetic analyses of HIV-1 env sequences demonstrate limited compartmentalization in breast milk and suggest viral replication within the breast that increases with mastitis.

Soren Gantt, Jacquelyn Carlsson, Laura Heath, Marta E Bull, Avinash K Shetty, Junior Mutsvangwa, Georgina Musingwini, Godfrey Woelk, Lynn S Zijenah, David A Katzenstein, James I Mullins, Lisa M Frenkel
Author Information
  1. Soren Gantt: Department of Pediatrics, Seattle Children's Hospital Research Institute, 1900 Ninth Ave., Seattle, WA. 98101-1304, USA. sgantt@uw.edu
PMID: 20660189 DOI: 10.1128/JVI.00543-10

Abstract

The concentration of human immunodeficiency virus type 1 (HIV-1) is generally lower in breast milk than in blood. Mastitis, or inflammation of the breast, is associated with increased levels of milk HIV-1 and risk of mother-to-child transmission through breastfeeding. We hypothesized that mastitis facilitates the passage of HIV-1 from blood into milk or stimulates virus production within the breast. HIV-1 env sequences were generated from single amplicons obtained from breast milk and blood samples in a cross-sectional study. Viral compartmentalization was evaluated using several statistical methods, including the Slatkin and Maddison (SM) test. Mastitis was defined as an elevated milk sodium (Na(+)) concentration. The association between milk Na(+) and the pairwise genetic distance between milk and blood viral sequences was modeled using linear regression. HIV-1 was compartmentalized within milk by SM testing in 6/17 (35%) specimens obtained from 9 women, but all phylogenetic clades included viral sequences from milk and blood samples. Monotypic sequences were more prevalent in milk samples than in blood samples (22% versus 13%; P = 0.012), which accounted for half of the compartmentalization observed. Mastitis was not associated with compartmentalization by SM testing (P = 0.621), but Na(+) was correlated with greater genetic distance between milk and blood HIV-1 populations (P = 0.041). In conclusion, local production of HIV-1 within the breast is suggested by compartmentalization of virus and a higher prevalence of monotypic viruses in milk specimens. However, phylogenetic trees demonstrate extensive mixing of viruses between milk and blood specimens. HIV-1 replication in breast milk appears to increase with inflammation, contributing to higher milk viral loads during mastitis.

Associated Data

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Grants

  1. R01 AI066922/NIAID NIH HHS
  2. P30 AI27757/NIAID NIH HHS
  3. T32 HD07233/NICHD NIH HHS
  4. T32 HD007233/NICHD NIH HHS
  5. R21 AI065288/NIAID NIH HHS
  6. KL2 RR025015/NCRR NIH HHS
  7. P30 AI027757/NIAID NIH HHS

MeSH Term

Base Sequence
Breast Feeding
Cross-Sectional Studies
DNA Primers
DNA, Viral
Female
Genes, env
HIV Infections
HIV-1
Humans
Infant
Infant, Newborn
Infectious Disease Transmission, Vertical
Mastitis
Milk, Human
Molecular Sequence Data
Phylogeny
Pregnancy
Pregnancy Complications, Infectious
Viral Load
Viremia
Virus Replication

Chemicals

DNA Primers
DNA, Viral
Journal Article Research Support, N.I.H., Extramural

Word Cloud

Created with Highcharts 10.0.0milkHIV-1breastbloodsequencescompartmentalizationwithinsamplesviralvirusMastitismastitisSMNa+specimensP=0concentrationinflammationassociatedproductionenvobtainedusinggeneticdistancetestingphylogenetichighervirusesdemonstratereplicationhumanimmunodeficiencytype1generallylowerincreasedlevelsriskmother-to-childtransmissionbreastfeedinghypothesizedfacilitatespassagestimulatesgeneratedsingleampliconscross-sectionalstudyViralevaluatedseveralstatisticalmethodsincludingSlatkinMaddisontestdefinedelevatedsodiumassociationpairwisemodeledlinearregressioncompartmentalized6/1735%9womencladesincludedMonotypicprevalent22%versus13%012accountedhalfobserved621correlatedgreaterpopulations041conclusionlocalsuggestedprevalencemonotypicHowevertreesextensivemixingappearsincreasecontributingloadsGeneticanalyseslimitedsuggestincreases

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