title: Breast milk from Tanzanian women has divergent effects on cell-free and cell-associated HIV-1 infection in vitro.
abstract: Transmission of HIV-1 during breastfeeding is a significant source of new pediatric infections in sub-Saharan Africa. Breast milk from HIV-positive mothers contains both cell-free and cell-associated virus; however, the impact of breast milk on HIV-1 infectivity remains poorly understood. In the present study, breast milk was collected from HIV-positive and HIV-negative Tanzanian women attending antenatal clinics in Dar es Salaam. Milk was analyzed for activity in vitro against both cell-free and cell-associated HIV-1. Potent inhibition of cell-free R5 and X4 HIV-1 occurred in the presence of milk from all donors regardless of HIV-1 serostatus. Inhibition of cell-free HIV-1 infection positively correlated with milk levels of sialyl-Lewis(X) from HIV-positive donors. In contrast, milk from 8 of 16 subjects enhanced infection with cell-associated HIV-1 regardless of donor serostatus. Milk from two of these subjects contained high levels of multiple pro-inflammatory cytokines including TNFα, IL-1β, IL-6, IL-8, MIP-1α, MIP-1β, MCP-1 and IP-10, and enhanced cell-associated HIV-1 infection at dilutions as high as 1∶500. These findings indicate that breast milk contains innate factors with divergent activity against cell-free and cell-associated HIV-1 in vitro. Enhancement of cell-associated HIV-1 infection by breast milk may be associated with inflammatory conditions in the mother and may contribute to infant infection during breastfeeding.
authors.affiliation: Department of Physiology, The Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, United States of America.
authors.forename: Magdalena A
authors.initials: MA
authors.lastname: Lyimo
authors.forename: Matilda Ngarina
authors.initials: MN
authors.lastname: Mosi
authors.forename: Molly L
authors.initials: ML
authors.lastname: Housman
authors.forename: Muhammad
authors.initials: M
authors.lastname: Zain-Ul-Abideen
authors.forename: Frederick V
authors.initials: FV
authors.lastname: Lee
authors.forename: Alexandra L
authors.initials: AL
authors.lastname: Howell
authors.forename: Ruth I
authors.initials: RI
authors.lastname: Connor
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D001942:Breast Feeding; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002474:Cell-Free System / Q000821:virology; D002648:Child; D016207:Cytokines / Q000378:metabolism; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D008895:Milk, Human / Q000378:metabolism / Q000821:virology*; D009844:Oligosaccharides / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen; D013636:Tanzania; D056189:Viral Tropism
chemical_list: D016207:Cytokines; D004279:DNA, Viral; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen