N. Kato et al., GENETIC DRIFT IN HYPERVARIABLE REGION-1 OF THE VIRAL GENOME IN PERSISTENT HEPATITIS-C VIRUS-INFECTION, Journal of virology, 68(8), 1994, pp. 4776-4784
The hypervariable region 1 (HVR1) of the putative second envelope glyc
oprotein (gp70) of hepatitis C virus (HCV) contains a sequence-specifi
c immunological B-cell epitope that induces the production of antibodi
es restricted to the specific viral isolate, and anti-HVR1 antibodies
are involved in the genetic drift of HVR1 driven by immunoselection (N
. Kato, H. Sekiya, Y. Ootsuyama, T. Nakazawa, M. Hijikata, S. Ohkoshi,
and K. Shimotohno, J. Virol. 67:3923-3930, 1993). We further investig
ated the sequence variability of the HCV genomic region that entirely
encodes the envelope proteins (gp35 and gp70); these sequences were de
rived from virus isolated during the acute and chronic phases of hepat
itis in one patient, and we found that HVR1 was a major site for genet
ic mutations in HCV after the onset of hepatitis. We carried out epito
pe mapping experiments using the HVR1 sequence derived from the acute
phase of hepatitis and identified two overlapping epitopes which are e
ach composed of 11 amino acids (positions 394 to 404 and 397 to 407).
The presence of two epitopes within HVR1 suggested that epitope shift
happened during the course of hepatitis. Four of six amino acid substi
tutions detected in HVR1 were located within the two epitopes. We furt
her examined the reactivities of anti-HVR1 antibodies to the substitut
ed amino acid sequences within the two epitopes. HVR1 variants in both
epitopes within the HVR1 escaped from anti-HVR1 antibodies that were
preexisting in the patient's serum.