Inhibition of hepatitis C virus infection by anti‐claudin‐1 antibodies is mediated by neutralization of E2–CD81–Claudin‐1 associations†

• DOI: 10.1002/hep.23445
• Publication Date: 2009-11-30T20:02:02Z
• Authors: Sophie E. Krieger; Mirjam B. Zeisel; Christopher Davis; Christine Thumann; Helen J. Harris; Eva K. Schnober; Christopher Mee; Eric Soulier; Cathy Royer; Mélanie Lambotin; Fritz Grunert; Viet Loan Dao Thi; Marlène Dreux; François‐Loïc Cosset; Jane A. McKeating; Catherine Schuster; Thomas F. Baumert
• Keywords: Claudin; CD81

The tight junction protein claudin-1 (CLDN1) has been shown to be essential for hepatitis C virus (HCV) entry—the first step of viral infection. Due the lack neutralizing anti-CLDN1 antibodies, role CLDN1 in entry process is poorly understood. In this study, we produced antibodies directed against human extracellular loops by genetic immunization and used these investigate mechanistic HCV an infectious cell culture system hepatocytes. Antibodies specific surface–expressed specifically inhibit infection a dose-dependent manner. CLDN1, scavenger receptor B1, CD81 show additive capacity compared with either agent alone. Kinetic studies anti-CD81 demonstrate that interactions both factors occur at similar time internalization process. Anti-CLDN1 binding envelope glycoprotein E2 permissive lines absence detectable CLDN1-E2 interaction. Using fluorescent-labeled fluorescence resonance energy transfer methodology, CD81-CLDN1 association. contrast, CLDN1-CLDN1 CD81-CD81 associations were not modulated. Taken together, our results targeting neutralize infectivity reducing association surface disrupting interactions. Conclusion: These further define function highlight new antiviral strategies E2-CD81-CLDN1 (HEPATOLOGY 2010.)