Nonstructural protein 5A does not contribute to the resistance of hepatitis C virus replication to interferon alpha in cell culture

The hepatitis C virus (HCV) subgenomic replicon system was used to study a possible involvement of nonstructural protein 5A (NS5A) in the mechanisms of HCV resistance to interferon alpha (IFN-α). A series of chimeric HCV replicons was constructed. In these replicons, the NS5A gene in the backbone of the Con1 replicon was swapped by corresponding fragments obtained from four IFN-α responder and four IFN-α nonresponder patients that had been infected with the same HCV AD78 strain. Experiments with transfected Huh7 cells did not reveal significant differences in sensitivity of HCV RNA replication to IFN-α in cell clones, bearing chimeric Con1/AD78 replicons with NS5A sequences from IFN responders and nonresponders. Thus, these data provide no evidence that the NS5A protein contributes to the resistance of HCV replication to IFN-α.