Genetic heterogeneity of the envelope 2 gene and eradication of hepatitis C virus after a second course of interferon‐α

The heterogeneity of the envelope 2 (E2) gene of the hepatitis C virus (HCV) was involved in the sensitivity of HCV to interferon‐α (IFN‐α). To assess the factors leading to virus eradication by IFN‐α, patients whose first treatment by IFN‐α failed and who had virus eradication after a second treatment were studied. These patients were paired with subjects in whom both treatments failed. The phosphorylation homology domain of the E2 gene (E2‐PHD) had no sequence variation between the two stages in both groups of patients. Therefore, this region has no clinical predictive value within a specific genotype. The hypervariable region 1 (HVR1) was analyzed by cloning and sequencing 20 clones per sample. Comparison of samples showed that the change in quasispecies induced by the first IFN‐α therapy could be associated with virus elimination obtained after a second treatment. The greater proportion of nonsynonymous mutations that was noted before the second treatment in responders suggest that pretherapeutic immune response is a major factor determining virus elimination and that the immune status of these patients changed between the first and the second treatment. J. Med. Virol. 68:221–228, 2002. © 2002 Wiley‐Liss, Inc.