Effects of adenovirus E1A protein on interferon-signaling.

We have previously shown that adenovirus E1A proteins can block interferon-alpha (IFN-alpha)-signalling. 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-expressing HeLa cell line IFN-gamma failed to induce the synthesis of IRF-1 mRNA. This failure was due to a block in activation of the crucial trans-acting factor, GAF, which in turn was due to the lack of IFN-gamma-activated tyrosine phosphorylation of the STAT1 alpha protein in E1A-expressing cells. The above defect could be attributed to a reduced level of STAT1 alpha protein. The level of p48 protein, which is required for IFN-alpha signaling, was also lowered. However, the level of lak-1 protein, one of the tyrosine kinases necessary for both IFN-alpha and IFN-gamma signalling, was comparable in the E1A-expressing and the control cells. These results indicate that the observed inhibition of IFN signalling in E1A-expressing cells is a consequence of a lower abundance of the necessary trnas-acting factors.