HUMORAL IMMUNE-RESPONSE TO HYPERVARIABLE REGION-1 OF THE PUTATIVE ENVELOPE GLYCOPROTEIN (GP70) OF HEPATITIS-C VIRUS

We recently found that alterations of amino acids in hypervariable reg ion 1 (HVR1) of the putative envelope glycoprotein (gp70) of hepatitis C virus (HCV) occurred sequentially in the chronic phase of hepatitis at intervals of several months. This finding suggests that mutations in HVR1 are involved in the mechanism of persistent chronic HCV infect ion involving escape from the immunosurveillance system. To explore th is possibility, we examined the humoral immune response to HVR1 with o ur assay system, in which immunoprecipitation was carried out with ser a from patients by using an HVR1 (27-amino-acid) dihydrofolate reducta se fusion protein synthesized by in vitro transcription and translatio n. Results showed that HVR1 contains a sequence-specific immunological epitope that induces the production of antibodies restricted to the s pecific viral isolate. Furthermore, analysis of the kinetics of the ap pearance of antibodies in two patients with chronic hepatitis, with wh om successive alterations of amino acids of HVR1 have been observed, s howed that the titers of anti-HVR1 antibodies usually reached maximal levels several months after the isolation of HCV having the specific s equence of HVR1. This observation suggests that anti-HVR1 antibodies a re involved in the genetic drift of HVR1 (minor antigenic variation) b y immunoselection. However, the coexistence of HVR1 as an antigen and its specific antibody was sometimes observed. The possibility that HVR 1 acts as a neutralizing epitope is discussed.