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Updated: Aug 10, 2026
A Protocol for Analyzing Hepatitis C Virus Replication
Published on: June 26, 2014
L-SIGN (CD 209L) is a liver-specific capture receptor for hepatitis C virus
Jason P Gardner1, Robert J Durso, Robert R Arrigale
1Progenics Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA. jgardner@progenics.com
Insights
Hepatitis C virus (HCV) infection may be facilitated by L-SIGN, a liver-specific receptor. L-SIGN and DC-SIGN bind HCV, potentially impacting viral infection and immunity.
Area of Science:
- Virology
- Immunology
- Hepatology
Background:
- Hepatitis C virus (HCV) affects nearly 3% of the global population, causing significant liver disease.
- The liver-specific mechanism of HCV infection is not fully understood due to the lack of identified receptors that bind viral glycoproteins.
- Liver/lymph node-specific intercellular adhesion molecule-3-grabbing integrin (L-SIGN) and dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) are lectins expressed in the liver and dendritic cells, respectively.
Purpose of the Study:
- To investigate the role of L-SIGN and DC-SIGN as potential cellular receptors for Hepatitis C virus.
- To determine if L-SIGN and DC-SIGN can bind naturally occurring HCV and identify the viral components involved in this interaction.
Main Methods:
- Virus-binding assays were employed to test the interaction between L-SIGN, DC-SIGN, and HCV.
- The binding was further characterized using inhibitors such as mannan, calcium chelators, and antibodies targeting the lectin domain of SIGN molecules.
Main Results:
- L-SIGN and DC-SIGN were demonstrated to specifically bind naturally occurring HCV found in infected individuals' sera.
- The binding interaction was confirmed to be mediated by the HCV envelope glycoprotein E2.
- Binding was inhibited by mannan, calcium chelators, and antibodies against the lectin domain of L-SIGN and DC-SIGN.
Conclusions:
- L-SIGN functions as a liver-specific receptor for Hepatitis C virus.
- L-SIGN and DC-SIGN likely play crucial roles in the processes of HCV infection and the host's immune response.
Abstract:
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.
