GENETIC ALTERATIONS OF THE PUTATIVE ENVELOPE PROTEINS ENCODING REGIONOF THE HEPATITIS-C VIRUS IN THE PROGRESSION TO RELAPSED PHASE FROM ACUTE HEPATITIS - HUMORAL IMMUNE-RESPONSE TO HYPERVARIABLE REGION-1

Hypervariable region I (HVRI) of the putative second envelope glycopro tein (gp70) of hepatitis C virus (HCV) undergoes sequential alteration s at intervals of several months during the chronic phase of hepatitis . To evaluate the implications of sequence variability in HVRI of HCV, we investigated the sequence variability of the whole envelope-protei n (gp35 and gp70)-coding regions of HCV genome derived from patient M in acute and relapsed phases (8-month interval) of hepatitis. From thi s analysis, we found that a Leu (position 405) in HVRI substituted to Pro, and that 4 additional substitutions could be detected in gp70 dur ing the relapsed phase. Sequence-specific antibody against HVRI derive d from patient M was first detected in the serum at 8 months after the onset of hepatitis, but no other specific antibodies against peptides containing amino-acid position(s) substituted in regions other than H VRI could be detected. Epitope mapping using the sequence of HVRI deri ved from the acute phase of hepatitis was also performed, and a B-cell epitope (positions 397 to 407) of 11 amino acids was identified. Howe ver, the Pro variant at position 405 did not display an escape pattern from the antibody produced at 8 months after the onset. In addition, we demonstrated the existence of important amino-acid residue position s which are recognized by the anti-HVRI antibody produced in patient M using introduction point mutations within HVRI. (C) 1994 Wiley-Liss, Inc.