RT Journal Article
SR Electronic
T1 L-SIGN (CD 209L) is a liver-specific capture receptor for hepatitis C virus
JF Proceedings of the National Academy of Sciences
JO Proc Natl Acad Sci USA
FD National Academy of Sciences
SP 4498
OP 4503
DO 10.1073/pnas.0831128100
VO 100
IS 8
A1 Gardner, Jason P.
A1 Durso, Robert J.
A1 Arrigale, Robert R.
A1 Donovan, Gerald P.
A1 Maddon, Paul J.
A1 Dragic, Tatjana
A1 Olson, William C.
YR 2003
UL http://www.pnas.org/content/100/8/4498.abstract
AB Hepatitis C virus (HCV) infects nearly 3% of the population of the world and is a major cause of liver disease. However, the mechanism whereby the virus targets the liver for infection remains unknown, because none of the putative cellular receptors for HCV are both expressed specifically in the liver and capable of binding HCV envelope glycoproteins. Liver/lymph node-specific intercellular adhesion molecule-3-grabbing integrin (L-SIGN) is a calcium-dependent lectin expressed on endothelial cells of liver and lymph nodes. Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), a homologous molecule expressed on dendritic cells, binds HIV and promotes infection. By using a virus-binding assay, we demonstrate that L-SIGN and DC-SIGN specifically bind naturally occurring HCV present in the sera of infected individuals. Further studies demonstrate that binding is mediated by the HCV envelope glycoprotein E2 and is blocked by specific inhibitors, including mannan, calcium chelators, and Abs to the lectin domain of the SIGN molecules. Thus, L-SIGN represents a liver-specific receptor for HCV, and L-SIGN and DC-SIGN may play important roles in HCV infection and immunity. LDL,low-density lipoprotein;ICAM,intercellular adhesion molecule;DC-SIGN,dendritic cell-specific ICAM-3-grabbing nonintegrin;HCV,hepatitis C virus;LSEC,liver sinusoidal endothelial cell;L-SIGN,liver/lymph node-specific ICAM-3-grabbing nonintegrin