Genetic heterogeneity of the NS5A gene of hepatitis C virus and early response to interferon-alpha.

The double-stranded RNA-activated protein kinase-binding domain (PKRbd) of the NS5A gene of hepatitis C virus (HCV) was studied by the cloning and sequencing method, in HCV-infected patients who had a primary resistance to treatment with interferon (IFN)-alpha (early nonresponders). Patients whose virus load decreased by >or=0.5 log (early responders) were similarly analyzed. In the 2 groups, the PKRbd evolved similarly over the first 24 h. Selection of resistant HCV variants is unlikely to explain primary resistance to IFN-alpha.