Epitopes described in "Monoclonal anti-claudin 1 antibodies prevent hepatitis C virus infection of primary human hepatocytes."

Article Authors:Isabel Fofana; Sophie E Krieger; Fritz Grunert; Sandra Glauben; Fei Xiao; Samira Fafi-Kremer; Eric Soulier; Cathy Royer; Christine Thumann; Christopher J Mee; Jane A McKeating; Tatjana Dragic; Patrick Pessaux; Francoise Stoll-Keller; Catherine Schuster; John Thompson; Thomas F Baumert
Article Title:Monoclonal anti-claudin 1 antibodies prevent hepatitis C virus infection of primary human hepatocytes.
Reference Detail
Reference ID:1020861
Abstract: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.
Reference Type:Literature
PubMed ID:20685314
Journal Volume:139
Article Pages:953-64, 964.e1-4
Journal ISSN:0016-5085
Article Chemical List:Antibodies, Monoclonal;Antiviral Agents;CLDN1 protein, human;Claudin-1;Epitopes;Membrane Proteins
Article MeSH List:Animals; Antibodies, Monoclonal(metabolism; pharmacology; toxicity); Antibody Specificity; Antiviral Agents(metabolism; pharmacology; toxicity); Binding Sites, Antibody; Binding, Competitive; CHO Cells; Cell Survival(drug effects); Claudin-1; Cricetinae; Cricetulus; Dose-Response Relationship, Drug; Epitopes; Genotype; Hep G2 Cells; Hepacivirus(drug effects; genetics; pathogenicity); Hepatitis C(immunology; prevention & control); Hepatocytes(drug effects; immunology; virology); Humans; Membrane Proteins(antagonists & inhibitors; immunology); Virus Internalization(drug effects)
Curation Last Updated:2014-10-03 22:13:17