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

G Rappocciolo, FJ Jenkins, HR Hensler… - The Journal of …, 2006 - journals.aai.org
G Rappocciolo, FJ Jenkins, HR Hensler, P Piazza, M Jais, L Borowski, SC Watkins
The Journal of Immunology, 2006journals.aai.org
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 …
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.
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