Abstract
Mother-to-child transmission of human immunodeficiency virus-1 (HIV-1) occurs frequently via breast-feeding. HIV-1 targets DC-SIGN+ dendritic cells (DCs) in mucosal areas that allow efficient transmission of the virus to T cells. Here, we demonstrate that the epithelial mucin MUC1, abundant in milk, efficiently bound to DC-SIGN on DC. The O-linked glycans within the mucin domain contained Lewis X structures, that were specifically recognized by the receptor. Interestingly, MUC1 prevented DC-SIGN-mediated transmission of HIV-1 from DCs to CD4+ T cells. We hypothesize that repetitive units of Lewis X, within the mucin domain, play an important role in inhibiting transmission of HIV-1 from mother to child.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / physiology
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CD4-Positive T-Lymphocytes / virology*
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CHO Cells
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Cell Adhesion Molecules / immunology
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Cell Adhesion Molecules / metabolism
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Cricetinae
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Cricetulus
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Dendritic Cells / physiology
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Dendritic Cells / virology*
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Female
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HIV Envelope Protein gp120 / physiology
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HIV Infections / immunology
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HIV Infections / transmission*
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HIV-1 / physiology*
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Humans
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Infectious Disease Transmission, Vertical
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Lectins, C-Type / immunology
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Lectins, C-Type / metabolism
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Lewis X Antigen / immunology
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Milk, Human / metabolism*
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Mucin-1 / physiology*
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Pregnancy
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Receptors, Cell Surface / immunology
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Receptors, Cell Surface / metabolism
Substances
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Cell Adhesion Molecules
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DC-specific ICAM-3 grabbing nonintegrin
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HIV Envelope Protein gp120
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Lectins, C-Type
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Lewis X Antigen
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MUC1 protein, human
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Mucin-1
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Receptors, Cell Surface