Differential effect of interferon on hepatitis C virus 1b quasispecies in the nonstructural protein 5A gene

A close correlation was reported between amino acid mutations in the nonstructural protein 5A (interferon [IFN] sensitivity-determining region [ISDR]) of hepatitis C virus (HCV)-1b and the response to IFN therapy. The dynamic change of ISDR quasispecies during IFN treatment was investigated in 22 patients. In 18 nonresponders, the number of ISDR mutations in major quasispecies decreased after therapy (P=.039). In each nonresponder, the percentage of wild-type (no mutations in the ISDR) quasispecies increased after treatment (P=.008), whereas the percentages of intermediate- (1-3 mutations) and mutant-type (>/=4 mutations) quasispecies decreased (P=.037 and P=.043, respectively). No mutant-type quasispecies were detected after therapy. Four complete responders had only quasispecies with >/=3 mutations before therapy. Thus, HCVs have fewer mutations in the ISDR after IFN therapy than those before therapy. These IFN-resistant HCVs were already present before therapy as minor quasispecies and were selected by IFN in nonresponders.