Antibody responses to hepatitis C virus hypervariable region 1: Evidence for cross-reactivity and immune-mediated sequence variation

Mario U. Mondelli, Antonella Cerino, Antonella Lisa, Sabrina Brambilla, Laura Segagni, Agostino Cividini, Morena Bissolati, Gabriele Missale, Giorgio Bellati, Annalisa Meola, Bruno Bruniercole, Alfredo Nicosia, Giovanni Galfrè, Enrico Silini

Research output: Contribution to journalArticlepeer-review


Sequence heterogeneity of hepatitis C virus (HCV) is unevenly distributed along the genome, and maximal variation is confined to a short sequence of the HCV second envelope glycoprotein (E2), designated hypervariable region 1 (HVR1), whose biological function is still undefined. We prospectively studied serological responses to synthetic oligopeptides derived from HVR1 sequences of patients with acute and chronic HCV infection obtained at baseline and after a defined follow-up period. Extensive serological cross-reactivity for unrelated HVR1 peptides was observed in the majority of the patients. Antibody response was restricted to the IgG1 isotype and was focused on the carboxyterminal end of the HVR1 region. Cross- reactive antibodies could be readily elicited following immunization of mice with multiple antigenic peptides carrying HVR1 sequences derived from our patients. The vigor and heterogeneity of cross-reactive antibody responses were significantly higher in patients with chronic hepatitis compared with those with acute hepatitis and in patients infected with HCV type 2 compared with patients infected with other vital genotypes (predominantly type 1), which suggest that higher time-related HVR1 sequence diversification previously described for type 2 may result from immune selection. The finding of a statistically significant correlation between HVR1 sequence variation, and intensity, and cross-reactivity of humoral immune responses provided stronger evidence in support of the contention that HCV variant selection is driven by the host's immune pressure.

Original languageEnglish
Pages (from-to)537-545
Number of pages9
Issue number2
Publication statusPublished - 1999

ASJC Scopus subject areas

  • Hepatology


Dive into the research topics of 'Antibody responses to hepatitis C virus hypervariable region 1: Evidence for cross-reactivity and immune-mediated sequence variation'. Together they form a unique fingerprint.

Cite this