In natural infection, HCV1‐like antibodies appear to be infrequently elicited, with only 2.5% of sera obtained from chronically infected humans possessing this specificity.41 An explanation for the low frequency of HCV‐1‐like antibody specificity may lie in observations that the immunodominant N‐terminal HVR1 region occludes the CD81‐binding site,16 potentially impairing the ability of epitopes located in the 413‐421 region to engage B‐cell receptors. Here, CD81 is linked to infection.