EFFECTS OF ADENOVIRUS E1A PROTEIN ON INTERFERON-SIGNALING

We have previously shown that adenovirus EIA proteins can block interf eron-alpha (IFN-alpha)-signaling. In the current study, we examined if the same is true for IFN-gamma signaling. Cotransfection experiments showed that both 289R and 243R forms of E1A could block the expression of an IFN-gamma-inducible reporter gene. Similarly, in an E1A-express ing HeLa cell line IFN-gamma failed to induce the synthesis of IRF-1 m RNA. This failure was due to a block in activation of the crucial tran s-acting factor, GAF, which in turn was due to the lack of IFN-gamma-a ctivated tyrosine phosphorylation of the STAT1 alpha protein in E1A-ex pressing cells. The above defect could be attributed to a reduced leve l of STAT1 alpha protein. The level of p48 protein, which is required for IFN-alpha signaling, was also lowered. However, the level of Jak-1 protein, one of the tyrosine kinases necessary for both IFN-alpha and IFN-gamma signaling, was comparable in the E1A-expressing and the con trol cells. These results indicate that the observed inhibition of IFN signaling in E1A-expressing cells is a consequence of a lower abundan ce of the necessary trans-acting factors. (C) 1996 Academic Press, Inc .