Key message
Hepatitis C virus (HCV) requires human CD81 to enter liver cells. Here, we generated chimeras of human CD81 with related proteins. Our work highlights that not only virus binding CD81 regions, but also additional regions – including a cholesterol-coordinating residue - are essential for HCV infection.
Translational perspective
This study opens new avenues for the analysis of human variants of the HCV receptor CD81 with implications for the understanding of the divergent pathogenesis of HCV in infected individuals.