RESTORATION OF INTERFERON RESPONSES OF ADENOVIRUS E1A-EXPRESSING HT1080 CELL-LINES BY OVEREXPRESSION OF P48 PROTEIN

Here, we report that in two other E1A-expressing cell lines derived fr om the HT1080 cells, neither IFN-alpha nor IFN-gamma could induce the transcription of genes containing the IFN-stimulated response element (ISRE), In contrast, IFN-gamma-mediated signaling to the gamma-activat ed sequence was unimpaired in these cells. This dichotomy was due to a lowered level of functional p48 protein but not of STAT1 protein in t he E1A-expressing HT1080 cells, When p48 was overexpressed in those ce lls by stably transfecting a p48 expression vector, both types of IFN could effectively induce the transcription of ISRE-driven genes, Conse quently, IFN-cu was highly effective in inhibiting the replication of encephelomyocarditis virus in the E1A-expressing cells, which also ove rexpressed p48, These results reinforce the general conclusion that ad enovirus E1A proteins block IFN signaling pathways by lowering the fun ctional levels of one or more components of the trans-acting complexes that activate the transcription of IFN-stimulated genes.