Inhibition of the cellular response to interferons by products of the adenovirus type 5 E1A oncogene

• Published in: Nucleic acids research 1991-08, Vol.19 (16), p.4387-4393
• Main Authors: Ackrill, A M, Foster, G R, Laxton, C D, Flavell, D M, Stark, G R, Kerr, I M
• Format: Article
• Language: English
• Subjects: Adenovirus; Adenovirus Early Proteins; Adenoviruses, Human - genetics; DNA-Binding Proteins - biosynthesis; Gene Expression Regulation - physiology; genes; Genes, MHC Class II; HeLa Cells; Humans; interferon; Interferon Type I - antagonists & inhibitors; Interferon Type I - biosynthesis; Interferon-gamma - antagonists & inhibitors; Oncogene Proteins, Viral - biosynthesis; Oncogene Proteins, Viral - genetics; Oncogene Proteins, Viral - physiology; Precipitin Tests; Recombinant Fusion Proteins - biosynthesis; RNA, Double-Stranded - pharmacology; Transfection; Tumor Cells, Cultured
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/19.16.4387

Expression of the E1A oncogene of adenovirus type 5 inhibits the response of interferon (IFN)-inducible constructs to Type I (alpha,beta) and II (gamma) IFNs in transient transfection assays. In human cell lines stably expressing E1A mRNA and protein acquisition of an antiviral state and the induction of a number of genes in response to alpha- and gamma-IFNs is inhibited. A short IFN-stimulable response element (ISRE) present in the 5' flanking region of a number of genes mediates induction by alpha- and gamma-IFNs. In cells expressing E1A there is a substantial reduction in the levels of the ISRE-binding factors E and M, inducible by alpha-IFN, and of factor G, inducible by gamma-IFN. In E1A-expressing cells the E alpha subunit of factor E is activated normally in response to alpha-IFN; the defect is in the production or activation of the E gamma subunit. The inhibitory activity of E1A is lost upon deletion of the CR1 domain. The induction of HLA class II genes by gamma-IFN, which involves a different DNA response element(s), and of beta-IFN mRNA in response to double-stranded RNA are also inhibited by E1A. An essential component(s) of a number of signalling pathways must, therefore, be subject, directly or indirectly, to inhibition by E1A.