Abstract
Infection of T cells by HIV-1 can occur through binding of virus to dendritic cell (DC)-specific ICAM-3 grabbing nonintegrin (DC-SIGN) on dendritic cells and transfer of virus to CD4+ T cells. Here we show that a subset of B cells in the blood and tonsils of normal donors expressed DC-SIGN, and that this increased after stimulation in vitro with interleukin 4 and CD40 ligand, with enhanced expression of activation and co-stimulatory molecules CD23, CD58, CD80, and CD86, and CD22. The activated B cells captured and internalized X4 and R5 tropic strains of HIV-1, and mediated trans infection of T cells. Pretreatment of the B cells with anti-DC-SIGN monoclonal antibody blocked trans infection of T cells by both strains of HIV-1. These results indicate that DC-SIGN serves as a portal on B cells for HIV-1 infection of T cells in trans. Transmission of HIV-1 from B cells to T cells through this DC-SIGN pathway could be important in the pathogenesis of HIV-1 infection.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Acquired Immunodeficiency Syndrome / etiology
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Acquired Immunodeficiency Syndrome / pathology
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Acquired Immunodeficiency Syndrome / physiopathology
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Antigens, CD / analysis
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B-Lymphocytes / chemistry*
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B-Lymphocytes / drug effects
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B-Lymphocytes / pathology
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B-Lymphocytes / virology
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Blood Cells / chemistry
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Blood Cells / pathology
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Blood Cells / virology
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CD4-Positive T-Lymphocytes / chemistry
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CD4-Positive T-Lymphocytes / physiology
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CD4-Positive T-Lymphocytes / virology*
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CD40 Ligand / pharmacology
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Cell Adhesion Molecules / genetics
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Cell Adhesion Molecules / metabolism*
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HIV Infections / immunology*
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HIV Infections / physiopathology
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HIV-1 / pathogenicity*
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HIV-1 / physiology
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Humans
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Interleukin-4 / pharmacology
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Lectins, C-Type / genetics
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Lectins, C-Type / metabolism*
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Lymphocyte Activation / physiology
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Palatine Tonsil / chemistry
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Palatine Tonsil / pathology
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Palatine Tonsil / virology
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Protein Binding
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RNA, Messenger / analysis
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RNA, Messenger / genetics
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism*
Substances
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Antigens, CD
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CLEC4M protein, human
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Cell Adhesion Molecules
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Lectins, C-Type
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RNA, Messenger
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Receptors, Cell Surface
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CD40 Ligand
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Interleukin-4