Activation of the Jak-Stat pathway in cells that exhibit selective sensitivity to the antiviral effects of IFN-beta compared with IFN-alpha

We determined whether selective activation of components of the Jak-Stat pa thway by different type I interferons (IFN) occurs in human myocardial fibr oblasts that exhibit much higher sensitivity to the antiviral effects of IF N-beta than of IFN-alpha. Similar levels of activation of the Tyk2 kinase a nd the Stat3 transcription factor were induced in response to either IFN-be ta or IFN-alpha treatment. However, activation of the Jak1 tyrosine kinase was detectable only in IFN-beta-treated but not IFN-alpha-treated cells. Co nsistent with this, tyrosine phosphorylation of Stat1 and Stat2 and formati on of the IFN-stimulated gene factor 3 (ISGF3) complex occurred to a much h igher degree in response to IFN-beta stimulation. These findings demonstrat e that differential activation of distinct components of the Jak-Stat pathw ay by different type I IFN can occur. Furthermore, they strongly suggest th at such selective activation accounts for the occurrence of differences in the antiviral properties of distinct type I IFN in certain cell types.