Clearance of persistent hepatitis C virus infection using a claudin-1-targeting monoclonal antibody

Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis and cancer(1). Cell entry of HCV(2) and other pathogens(3-5) is mediated by tight junction (TJ) proteins, but successful therapeutic targeting of TJ proteins has not been reported yet. Using a human liver-chimeric mouse model(6) we show that a monoclonal antibody specific for TJ protein claudin-1(7) eliminates chronic HCV infection without detectable toxicity. This antibody inhibits HCV entry, cell-cell transmission and virus-induced signaling events. Antibody treatment reduces the number of HCV-infected hepatocytes in vivo, highlighting the need for de novo infection via host entry factors to maintain chronic infection. In summary, we demonstrate that an antibody targeting a virus receptor can cure chronic viral infection and uncover TJ proteins as targets for antiviral therapy.