L-SIGN (CD 209L) is a liver-specific capture receptor for hepatitis C virus.
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.
Gardner
Jason P
JP
Progenics Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA. jgardner@progenics.com
Durso
Robert J
RJ
Arrigale
Robert R
RR
Donovan
Gerald P
GP
Maddon
Paul J
PJ
Dragic
Tatjana
T
Olson
William C
WC
D001483:Base Sequence; D001665:Binding Sites; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D018076:DNA, Complementary / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D006367:HeLa Cells; D016174:Hepacivirus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D006526:Hepatitis C / Q000821:virology*; D006801:Humans; D066298:In Vitro Techniques; D037181:Lectins, C-Type / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000821:virology*; D012367:RNA, Viral / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D011991:Receptors, Virus / Q000502:physiology*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000235:genetics / Q000502:physiology
C433029:CLEC4M protein, human; D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D004279:DNA, Viral; D037181:Lectins, C-Type; D012367:RNA, Viral; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus