N. Kato et al., HUMORAL IMMUNE-RESPONSE TO HYPERVARIABLE REGION-1 OF THE PUTATIVE ENVELOPE GLYCOPROTEIN (GP70) OF HEPATITIS-C VIRUS, Journal of virology, 67(7), 1993, pp. 3923-3930
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.