DC-SIGN is a receptor for human herpesvirus 8 on dendritic cells and macrophages

J Immunol. 2006 Feb 1;176(3):1741-9. doi: 10.4049/jimmunol.176.3.1741.

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

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Antibodies, Monoclonal / metabolism
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / immunology
  • Cell Adhesion Molecules / metabolism*
  • Cell Line
  • Cell Line, Transformed
  • Dendritic Cells / metabolism*
  • Dendritic Cells / virology
  • Herpesviridae Infections / immunology
  • Herpesvirus 8, Human / metabolism*
  • Humans
  • Integrin alpha3beta1 / physiology
  • K562 Cells
  • Lectins, C-Type / genetics
  • Lectins, C-Type / immunology
  • Lectins, C-Type / metabolism*
  • Macrophages / metabolism*
  • Mannans / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology
  • Receptors, Cell Surface / metabolism*
  • Receptors, Virus / genetics
  • Receptors, Virus / immunology
  • Receptors, Virus / metabolism*

Substances

  • Antibodies, Monoclonal
  • Cell Adhesion Molecules
  • DC-specific ICAM-3 grabbing nonintegrin
  • Integrin alpha3beta1
  • Lectins, C-Type
  • Mannans
  • Receptors, Cell Surface
  • Receptors, Virus