VIRUS ISOLATE-SPECIFIC ANTIBODIES AGAINST HYPERVARIABLE REGION-1 OF THE HEPATITIS-C VIRUS 2ND-ENVELOPE PROTEIN, GP70

Hypervariable region 1 (HVR1), located in the N-terminal region of a p utative second envelope glycoprotein (gp70) of hepatitis C virus (HCV) , contains immunological B-cell epitopes which might be neutralizing e pitopes. To clarify whether B-cell epitopes within HVR1 are common amo ng virus isolates or specific for the homologous virus isolate, we exa mined the reactivities of sera from 53 patients with chronic hepatitis or hepatocellular carcinoma/liver cirrhosis against two different HVR 1 peptides (HVR1 I-1 and HVR1 Y-1) derived from patient I with sporadi c acute hepatitis and an asymptomatic carrier Y, respectively, using o ur original assay system for the detection of anti-HVR1 antibody. All patients examined had a history of blood transfusion. Most sera showed no reactivity with either HVR1 I-1 or HVR1 Y-1 peptide. Only seven an d fourteen serum samples reacted significantly, although weakly, with HVR1 I-1 and HVR1 Y-1 peptides, respectively, compared with the serum from patient I or asymptomatic carrier Y. The blood transfusions of mo st reactive cases had occurred more than thirty years earlier. Six cas es reacted with both HVR1 I-1 and HVR1 Y-1 peptides, but further analy sis revealed that only three cases reacted weakly with the peptide for either epitope I or II, identified within HVR1 I-1. These results ind icate that the B-cell epitopes within HVR1 are fairly specific for the homologous virus isolate, and this may represent a serious difficulty in the development of a vaccine against HCV.