Restoration of interferon responses of adenovirus E1A-expressing HT1080 cell lines by overexpression of p48 protein.
We have previously shown that both alpha interferon (IFN-alpha) and IFN-gamma signaling pathways are blocked in HeLa cells expressing the adenovirus E1A proteins (G. T. Leonard and G. C. Sen, Virology 224:25-33, 1996). Here, we report that in two other E1A-expressing cell lines derived from 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-activated sequence was unimpaired in these cells. This dichotomy was due to a lowered level of functional p48 protein but not of STAT1 protein in the E1A-expressing HT1080 cells. When p48 was overexpressed in those cells by stably transfecting a p48 expression vector, both types of IFN could effectively induce the transcription of ISRE-driven genes. Consequently, IFN-alpha was highly effective in inhibiting the replication of encephelomyocarditis virus in the E1A-expressing cells, which also overexpressed p48. These results reinforce the general conclusion that adenovirus E1A proteins block IFN signaling pathways by lowering the functional levels of one or more components of the trans-acting complexes that activate the transcription of IFN-stimulated genes.
Leonard
G T
GT
Department of Molecular Biology, The Cleveland Clinic Foundation, Research Institute, Ohio 44195, USA.
Sen
G C
GC
D017500:Adenovirus E1A Proteins / Q000235:genetics*; D000998:Antiviral Agents / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000235:genetics*; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D006801:Humans; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D015398:Signal Transduction; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured
D017500:Adenovirus E1A Proteins; D000998:Antiviral Agents; D004268:DNA-Binding Proteins; C494227:IRF9 protein, human; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha; D015534:Trans-Activators; D014157:Transcription Factors; D007371:Interferon-gamma