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

A close correlation was reported between amino acid mutations in the nonstr uctural 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 pa tients. In 18 nonresponders, the number of ISDR mutations in major quasispe cies decreased after therapy (P = .039). In each nonresponder, the percenta ge of wild-type (no mutations in the ISDR) quasispecies increased after tre atment (P = .008), whereas the percentages of intermediate- (1-3 mutations) and mutant-type (greater than or equal to 4 mutations) quasispecies decrea sed (P = .037 and P = .043, respectively). No mutant-type quasispecies were detected after therapy. Four complete responders had only quasispecies wit h greater than or equal to 3 mutations before therapy. Thus, HCVs have fewe r mutations in the ISDR after IFN therapy than those before therapy. These IFN-resistant HCVs were already present before therapy as minor quasispecie s and were selected by IFN in nonresponders.