C Type Lectin Lsectin As Hepatitis C Virus Receptor Systems Analysis

Hepatitis C virus (HCV) is a major cause of liver disease. However the detail mechanism of hepatocyte infection remains unknown. A novel C-type lectin LSECtin is expressed on the liver and lymph node sinusoidal endothelial cell and has a similar structure to DC-SIGNR, a binding receptor for HCV. Previous report suggest that LSECtin may bind HCV by interacting with glycoprotein E2 and function as a capture receptor in a manner similar to DC-SIGNR . We used three methods including the soluble E2 glycoprotein binding assay, the HCV pseudotype particles binding assay and the HCV virions binding assay to evidence the hypothesis that HCV binds to LSECtin. Moreover, similar protein structure and expression profile of LSECtin and DC-SIGNR urged us to investigate whether there is an interaction between LSECtin and DC-SIGNR and how the interaction affects the adhesion of HCV. The interaction between LSECtin and DC-SIGNR was studied by co-immunoprecipitation and cell adhesion assays. Here we demonstrated that the E2 glycoprotein and HCV pseudotype particles bind the LSECtin expressed cells, which was blocked by EGTA but not mannan. Furthermore HCV virions present in the sera of infected patients confirmed the interaction. We also showed that LSECtin interacts with DC-SIGNR, in which the neck region of LSECtin is necessary for the interaction. The interaction may induce the decrease of HCV affinity binding to the DC-SIGNR and LSECtin co-expressed cells. This study indicates LSECtin is a novel to the binding receptors on the liver node sinusoidal endothelial cells and that there is the more complicated mechanism of HCV infection.