Humoral immune response to hypervariable region 1 of a hepatitis C viral envelope glycoprotein (gp70) obtained from an asymptomatic carrier

Hypervariable region 1 (HVR1) of hepatitis C virus (HCV) shows striking genetic alterations, even within a period of several months, in patients with chronic hepatitis (CH). Recently, using our developed assay system for detection anti-HVR1 antibodies, we found that HVR1 acts as an immunological epitope, and that altered HVR1 variants can escape from pre-existing antibodies. This suggests that genetic alterations of HVR1 are involved in persistent HCV infection. Furthermore, we observed that HVR1 from an asymptomatic carrier, one who showed normal liver functions, also underwent time-dependent genetic alteration. We have now examined the humoral immune response to five HVR1 variants obtained from an asymptomatic carrier. The results show that sequence-specific anti-HVR1 antibodies can be detected even in a carrier as they are in patients with CH, although anti-HVR1 antibody titers are comparatively low. In addition, we found one HVR1 variant, obtained at the last time point, that was not recognized by the pre-existing antibodies in this carrier. However, the remaining four HVR1 variants reacted equally with sera from the carrier. The possibility that genetic alterations of HVR1 allow HCV to escape from the immunosurveillance system is discussed.