Rapid Changes in Hepatitis C Virus Quasispecies Produced by a Single Dose of IFN- α in Chronically Infected Patients

Abstract

The effects of a single dose of 3 international megaunits of interferon-α2b (IFN-α2b) on hepatitis C virus (HCV) load and quasispecies were examined 24 h after administration in 12 previously untreated, chronically infected patients. All patients had viremia loads appreciably reduced relative to baseline values, thus confirming that the viral load is rapidly affected by IFN-α2b. Five patients also exhibited changes in plasma HCV quasispecies composition that were clearly evident by single-strand conformation polymorphism, analysis, thus indicating that one dose of IFN-α2b may suffice to produce rapid perturbations in the genetic heterogeneity of circulating HCV. Prior to IFN-α2b administration, 3 patients exhibited viral quasispecies differences between plasma and peripheral blood mononuclear cells (PBMC). Interestingly, in 2 such patients, the viral quasispecies found in the 24-h plasma resembled that in the pre-IFN PBMC. The latter finding raises the possibility that in these patients, the differences in quasispecies composition between pre-IFN and post-IFN plasma resulted from increased representation of lymphoid tissue-originated variants in the latter sample, possibly because of poor sensitivity to IFN-α2b of HCV replication in the lymphoid compartment.