Functional and immunogenic characterization of diverse HCV glycoprotein E2 variants.

•High resolution mapping of HVR1 and glycosylation sites’ impact on CD81 binding, antibody binding and virus neutralization.•Viral mutants lacking HVR1 and selected glycosylation sites are functional.•These mutants expose the viral CD81 binding site and conserved cross-neutralization epitopes.•E2 proteins with these mutations induce cross-binding and non-interfering antibodies in mice.