Hypervariable region 1 of hepatitis C virus: immunological decoy or biologically relevant domain?

The hypervariable region 1 (HVR1) of the E2 protein of hepatitis C virus (H CV) is highly heterogeneous and is responsible for significant inter- and i ntro-individual variation of the infecting virus, which may represent an im portant pathogenetic mechanism leading to escape and persistent infection. Moreover, a binding site for neutralizing antibodies (Ab) has been allegedl y identified in this region. Prospective studies of serological responses t o synthetic oligopeptides derived from HVR1 sequences of patients with acut e and chronic HCV infection showed extensive serological cross-reactivity f or unrelated HVR1 peptides in the majority of the patients. A significant c orrelation was found between HVR1 sequence variation, and intensity, and cr oss-reactivity of humoral immune responses providing strong evidence in sup port of the contention that HCV variant selection is driven by the host imm une pressure. Monoclonal Ab (mAb) generated following immunization of mice with peptides derived from natural HVR1 sequences also showed cross-reactiv ity for several HVR1 sequences attesting to the existence of conserved amin o acid motifs among different variants. These findings suggest that it is p ossible to induce a broadly cross-reactive immune response to HVR1 and that this mechanism can be used to generate protective immunity for a large rep ertoire of HCV variants. (C) 2001 Elsevier Science B.V. All rights reserved .