Effect of increasing dose of interferon on the evolution of hepatitis C virus 1b quasispecies

The effects of interferon therapy on hepatitis C virus (HCV) genome are sti ll controversial in terms of biological and clinical significance. Changes in the quasispecies of the hypervariable (HVR) and non-structural 5A (NS5A) regions of HCV 1b were evaluated in nine patients treated with increasing doses of interferon and five untreated controls. HCV quasispecies were anal yzed in HVR and NS5A by single-strand conformation polymorphism assay. The HVR quasispecies varied over time both in treated and untreated patients. H owever, at least one persistent strain was present in all patients. With lo w doses of interferon, variations in HVR complexity were found in seven of nine patients and in four patients new variants became detectable. A reduct ion in the heterogeneity of the HVR quasispecies was observed after increas e of the interferon dose. In contrast, NS5A profiles remained unmodified in all but three cases in which direct sequencing showed no changes in amino acid sequences of the predominant strain. The results suggest that interfer on sensitivity of some HCV strains may be dose dependent. The homogeneity o f NS5A pattern populations during treatment suggests that interferon exerts much less pressure on this region. J. Med. Virol. 60:133-138, 2000. (C) 20 00 Wiley-Liss, Inc.