IFN-α5 Mediates Stronger Tyk2-Stat-Dependent Activation and Higher Expression of 2′,5′-Oligoadenylate Synthetase Than IFN-α2 in Liver Cells

Interferon-α5 (IFN-α5) is the main IFN-α subtype expressed in the liver. Hepatitis C virus (HCV) infection is associated with low IFN-α5 mRNA levels, possibly reflecting an escape mechanism of the virus. In this work, we sought to compare IFN-α2 and IFN-α5 with respect to activation of early cell signaling cascades and induction of antiviral genes in the human hepatoma HepG2 and Huh7 cell lines. We found that the Tyr701 phosphorylation kinetics of Stat1 mediated by IFN stimulation was higher when cells were incubated with IFN-α5 than when using IFN-α2. Similarly, Tyr1054/1055 phosphorylation kinetics of Tyk2 were more intense after exposure to IFN-α5 than when using IFN-α2. Concomitantly, Tyr705 phosphorylation of Stat3 was higher after stimulation with IFN-α5 than with IFN-α2. In parallel to these findings, the mRNA levels of the antiviral IFN-inducible gene 2′,5′-oligoadenylate synthetase were higher in cell samples treated with IFN-α5 than with IFN-α2. These findings suggest that interaction of IFN-α5 ...