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Abstract

The viral life cycle of the hepatitis C virus (HCV) has been studied mainly using different in vitro cell culture models. Studies using pseudoviral particles (HCVpp) and more recently cell culture–derived virus (HCVcc) suggest that at least three host cell molecules are important for HCV entry in vitro: the tetraspanin CD81, the scavenger receptor class B member I, and the tight junction protein Claudin-1. Whether these receptors are equally important for an in vivo infection remains to be demonstrated. We show that CD81 is indispensable for an authentic in vivo HCV infection. Prophylactic treatment with anti-CD81 antibodies completely protected human liver-uPA-SCID mice from a subsequent challenge with HCV consensus strains of different genotypes. Administration of anti-CD81 antibodies after viral challenge had no effect. Conclusion: Our experiments provide evidence for the critical role of CD81 in a genuine HCV infection in vivo and open new perspectives for the prevention of allograft reinfection after orthotopic liver transplantation in chronically infected HCV patients. (HEPATOLOGY 2008;48:1761–1768.)