ANTIBODIES DIRECTED TO ENVELOPE PROTEINS OF HEPATITIS-C VIRUS OUTSIDEOF HYPERVARIABLE REGION-1

The relatively high variability of the hepatitis C virus (HCV) envelop e proteins El and 52 suggests that parts of these proteins other than the hypervariable region 1 (HVR1) might be involved in the induction o f virus neutralizing antibodies. To test this hypothesis, two HCV prot eins, pE1 and pE2 Delta, were generated by in vitro translation. They represent amino acids 174-337 of El and 411-688 of E2, respectively, o f isolate HCV-AD78; the protein pE2 Delta contained no HVR1. As a cont rol, protein pG.HVR1, which represents amino acids 384-410 of HVR1 of isolate HCV-AD78, was expressed separately. These three proteins were used in an immunoprecipitation assay to detect the presence of antivir al antibodies in sera of patients infected with the same isolate of HC V (HCV-AD78). Sera were obtained 4-8 months postinfection from patient s who later resolved an acute infection or developed chronic liver dis ease. A high prevalence of antibodies (up to 85.7%) against pE1 and pE 2 Delta could be detected in both groups of patients, suggesting that these forms of the HCV envelope proteins contain B-cell epitopes. The antibody responses against proteins pE1 and pE2 Delta did not differ s ignificantly between patients with resolving or chronic infection, whe reas antibodies against protein pG.HVR1 were associated with resolutio n of infection. Rabbit antisera raised against pE1 and pE2 Delta were tested for their ability to neutralize the binding of HCV to susceptib le cells in tissue cultures. The results suggested that although a few B-cell epitopes outside of HVR1 can induce virus neutralizing antibod ies, these antibodies are probably not associated with the resolution of infection. (C) 1998 Academic Press.