Function of the HCV E1 Envelope Glycoprotein in Viral Entry and Assembly

Abstract

HCV envelope glycoproteins, E1 and E2, are multifunctional proteins. Until recently, E2 glycoprotein was thought to be the fusion protein and was the focus of investigations. However, the recently obtained partial structures of E2 and E1 rather support a role for E1 alone or in association with E2 in HCV fusion. Moreover, they suggest that HCV harbors a new fusion mechanism, distinct from that of other members of the Flaviviridae family. In this context, E1 aroused a renewed interest. Recent functional characterizations of E1 revealed a more important role than previously thought in entry and assembly. Thus, E1 is involved in the viral genome encapsidation step and influences the association of the virus with lipoprotein components. Moreover, E1 modulates HCV–receptor interaction and participates in a late entry step potentially fusion. In this review, we outline our current knowledge on E1 functions in HCV assembly and entry.