DC-SIGN is a receptor for human herpesvirus 8 on dendritic cells and macrophages.
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.
Rappocciolo
Giovanna
G
Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, PA 15261, USA. giovanna@pitt.edu
Jenkins
Frank J
FJ
Hensler
Heather R
HR
Piazza
Paolo
P
Jais
Mariel
M
Borowski
Luann
L
Watkins
Simon C
SC
Rinaldo
Charles R
CR
D000328:Adult; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002461:Cell Line, Transformed; D003713:Dendritic Cells / Q000378:metabolism* / Q000821:virology; D006566:Herpesviridae Infections / Q000276:immunology; D019288:Herpesvirus 8, Human / Q000378:metabolism*; D006801:Humans; D039201:Integrin alpha3beta1 / Q000502:physiology; D020014:K562 Cells; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008351:Mannans / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011991:Receptors, Virus / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D039201:Integrin alpha3beta1; D037181:Lectins, C-Type; D008351:Mannans; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin