Topic Overview:
Hepatitis C virus (HCV) exacts a heavy toll on global health, causing acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Infection by this enveloped, single-stranded RNA virus is almost exclusively restricted to human hepatocytes, a phenomenon that can be attributed to HCV’s specific mode of entry into these cells. Infectious virions attach to the cell surface and associate with cellular receptors, including CD81 and SR-BI. In the presence of tight junction proteins claudin-1 (CLDN1) and occludin (OCLN), the bound virions then undergo clathrin-mediated endocytosis and traffic to endosomal compartments, where they undergo a conformational change and fuse with the cellular membrane to gain entry into the cell.

While CD81 and SR-BI are known to interact with viral envelope glycoproteins, CLDN1 and OCLN do not appear to directly interact with incoming virions, leaving their roles in HCV entry elusive. Wang will discuss his recent findings that human OCLN is an essential factor of HCV entry. He will also discuss unpublished results demonstrating that two novel peptides, derived from human claudin-1 and apoE, are potent inhibitors of HCV infection. These advances present an opportunity to develop novel therapeutics to combat HCV infection.