Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

BACKGROUND & AIMS: Hepatitis C virus (HCV) infection is a challenge to prevent and treat because of the rapid development of drug resistance and escape. Viral entry is required for initiation, spread, and maintenance of infection, making it an attractive target for antiviral strategies. The tight junction protein claudin-1 (CLDN1) has been shown to be required for entry of HCV into the cell. METHODS: Using genetic immunization, we produced 6 monoclonal antibodies against the host entry factor CLDN1. The effects of antibodies on HCV infection were analyzed in human cell lines and primary human hepatocytes. RESULTS: Competition and binding studies demonstrated that antibodies interacted with conformational epitopes of the first extracellular loop of CLDN1; binding of these antibodies required the motif W(30)-GLW(51)-C(54)-C(64) and residues in the N-terminal third of CLDN1. The monoclonal antibodies against CLDN1 efficiently inhibited infection by HCV of all major genotypes as well as highly variable HCV quasispecies isolated from individual patients. Furthermore, antibodies efficiently blocked cell entry of highly infectious escape variants of HCV that were resistant to neutralizing antibodies. CONCLUSIONS: Monoclonal antibodies against the HCV entry factor CLDN1 might be used to prevent HCV infection, such as after liver transplantation, and might also restrain virus spread in chronically infected patients.

Original publication

DOI

10.1053/j.gastro.2010.05.073

Type

Journal article

Journal

Gastroenterology

Publication Date

09/2010

Volume

139

Pages

953 - 964.e4

Keywords

Animals, Antibodies, Monoclonal, Antibody Specificity, Antiviral Agents, Binding Sites, Antibody, Binding, Competitive, CHO Cells, Cell Survival, Claudin-1, Cricetinae, Cricetulus, Dose-Response Relationship, Drug, Epitopes, Genotype, Hep G2 Cells, Hepacivirus, Hepatitis C, Hepatocytes, Humans, Membrane Proteins, Virus Internalization