title: Genetic analyses of HIV-1 env sequences demonstrate limited compartmentalization in breast milk and suggest viral replication within the breast that increases with mastitis.
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.
authors.affiliation: Department of Pediatrics, Seattle Children's Hospital Research Institute, 1900 Ninth Ave., Seattle, WA. 98101-1304, USA. sgantt@uw.edu
authors.forename: Soren
authors.initials: S
authors.lastname: Gantt
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Carlsson
authors.forename: Laura
authors.initials: L
authors.lastname: Heath
authors.forename: Marta E
authors.initials: ME
authors.lastname: Bull
authors.forename: Avinash K
authors.initials: AK
authors.lastname: Shetty
authors.forename: Junior
authors.initials: J
authors.lastname: Mutsvangwa
authors.forename: Georgina
authors.initials: G
authors.lastname: Musingwini
authors.forename: Godfrey
authors.initials: G
authors.lastname: Woelk
authors.forename: Lynn S
authors.initials: LS
authors.lastname: Zijenah
authors.forename: David A
authors.initials: DA
authors.lastname: Katzenstein
authors.forename: James I
authors.initials: JI
authors.lastname: Mullins
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Frenkel
mesh_terms: D001483:Base Sequence; D001942:Breast Feeding / Q000009:adverse effects; D003430:Cross-Sectional Studies; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D015752:Genes, env; D015658:HIV Infections / Q000150:complications* / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification* / Q000502:physiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008413:Mastitis / Q000150:complications* / Q000821:virology*; D008895:Milk, Human / Q000821:virology*; D008969:Molecular Sequence Data; D010802:Phylogeny; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000821:virology; D019562:Viral Load; D014766:Viremia / Q000150:complications / Q000821:virology; D014779:Virus Replication
chemical_list: D017931:DNA Primers; D004279:DNA, Viral