The hypervariable region 1 protein of hepatitis C-virus broadly reactive with sera of patients with chronic hepatitis C has a similar amino acid sequence with the consensus sequence

Hypervariable region 1 (HVR1) proteins of hepatitis C virus (HCV) have been reported to react broadly with sera of patients with HCV infection. Howeve r, the variability of the broad reactivity of individual HVR1 proteins has not been elucidated. We assessed the reactivity of 25 different HVR1 protei ns (genotype Ib) with sera of 81 patients with HCV infection (genotype 1b) by Western blot. HVR1 proteins reacted with 2-60 sera. The number of sera r eactive with each HVR1 protein significantly correlated with the number of amino acid residues identical to the consensus sequence defined by Puntorie ro et al. (G. Puntoriero, A. Lahm, S. Zucchelli, B. B. Ercole, R. Tafi, M. Penzzanera, M. U. Mondelli, R. Cortese, A. Tramontano, G. Galfre', and A. N icosia. 1998. EMBO J. 17, 3521-3533) (r = 0.561, P < 0.005). The most widel y reactive HVR1 protein, 12-22, had a sequence similar to the consensus seq uence. The peptide with C-terminal 13-amino-acids sequence of HVR1 protein 12-22 (NH2-CSFTSLFTPGPSQK) was injected into rabbits as an immunogen. The r abbit immune sera reacted with 9 of 25 HVR1 proteins of genotype 1b includi ng HVR1 protein 12-22 and with 3 of 12 proteins of genotype 2a. These resul ts indicate that the HVR1 protein broadly reactive with patients' sera has a sequence similar to the consensus sequence, can induce broadly reactive s era, and could be one of the candidate immunogens in a prophylactic vaccine against HCV. (C) 1999 Academic Press.