Abstract
Human herpesvirus 8 (HHV-8) causes Kaposi's sarcoma and pleural effusion lymphoma. In this study, we show that dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN; CD209) is a receptor for HHV-8 infection of myeloid DCs and macrophages. DC-SIGN was required for virus attachment to these cells and DC-SIGN-expressing cell lines. HHV-8 binding and infection were blocked by anti-DC-SIGN mAb and soluble DC-SIGN, and mannan, a natural ligand for DC-SIGN. Infection of DCs and macrophages with HHV-8 led to production of viral proteins, with little production of viral DNA, similar to HHV-8 infection of vascular endothelial cells. Infection of DCs resulted in down-regulation of DC-SIGN, a decrease in endocytic activity, and an inhibition of Ag stimulation of CD8+ T cells. We propose that DC-SIGN serves as a portal for immune dysfunction and oncogenesis caused by HHV-8 infection.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adult
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Antibodies, Monoclonal / metabolism
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Cell Adhesion Molecules / genetics
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Cell Adhesion Molecules / immunology
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Cell Adhesion Molecules / metabolism*
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Cell Line
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Cell Line, Transformed
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Dendritic Cells / metabolism*
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Dendritic Cells / virology
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Herpesviridae Infections / immunology
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Herpesvirus 8, Human / metabolism*
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Humans
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Integrin alpha3beta1 / physiology
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K562 Cells
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Lectins, C-Type / genetics
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Lectins, C-Type / immunology
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Lectins, C-Type / metabolism*
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Macrophages / metabolism*
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Mannans / metabolism
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / immunology
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Receptors, Cell Surface / metabolism*
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Receptors, Virus / genetics
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Receptors, Virus / immunology
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Receptors, Virus / metabolism*
Substances
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Antibodies, Monoclonal
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Cell Adhesion Molecules
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DC-specific ICAM-3 grabbing nonintegrin
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Integrin alpha3beta1
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Lectins, C-Type
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Mannans
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Receptors, Cell Surface
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Receptors, Virus