Human milk oligosaccharides reduce HIV-1-gp120 binding to dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN)

Patrick Hong, Milady R. Ninonuevo, Benhur Lee, Carlito B Lebrilla, Lars Bode

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

Breast-feeding is the predominant postnatal transmission route for HIV-1 infection in children. However, a majority of breast-fed infants do not become HIV-infected despite continuous exposure to the virus through their mothers' milk over many months. What protects some breast-fed infants from HIV-1 infection? HIV-1 entry across the infant's mucosal barrier is partially mediated through binding of the HIV-1 surface glycoprotein gp120 to dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN) on human dendritic cells. Lewis antigen glycans, present in human milk, bind to DC-SIGN and inhibit HIV-1 transfer to CD4+T lymphocytes. Human milk contains a high amount of unbound, complex oligosaccharides (5-10 g/l) that carry one or more Lewis antigen glycans, and we hypothesized that they compete with gp120 for DC-SIGN binding. Here, we show in two independent assays that physiological concentrations of human milk oligosaccharides significantly reduce gp120 binding to DC-SIGN by more than 80 %. These results may provide an additional explanation for the inhibitory effects of human milk on HIV-1 mother-to-child-transmission. Identifying the specific milk oligosaccharides that interact with DC-SIGN may guide the development of glycan-based drugs that prevent transmission of HIV-1 and other pathogens that use DC-SIGN as an entry point. However, blocking DC-SIGN may be a two-edged sword.

Original languageEnglish (US)
Pages (from-to)482-486
Number of pages5
JournalBritish Journal of Nutrition
Volume101
Issue number4
DOIs
StatePublished - 2009

Keywords

  • Breast-feeding
  • DC-SIGN
  • Dendritic cells
  • HIV-1
  • Human milk oligosaccharides

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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