Abstract
The recent development of functional models to analyze the early steps of the hepatitis C virus (HCV) life cycle has highlighted that HCV entry is a slow and complex multistep process involving the presence of several entry factors. Initial host cell attachment may involve glycosaminoglycans and the low-density lipoprotein receptor, after which the particle appears to interact sequentially with three entry factors: the scavenger receptor class B type I, the tetraspanin CD81 and the tight-junction protein claudin-1. Several serum components may also modulate HCV entry, while the recently discovered CD81 partner EWI-2wint can block the interaction of the viral particle with CD81, potentially preventing infection in the cell types in which it is expressed. After binding to the host cell, the HCV particle is internalized by clathrin-mediated endocytosis, with fusion likely occurring in early endosomes. This review summarizes our current knowledge on HCV entry.