Inhibition of the cellular response to interferons by products of the adenovirus type 5 E1A oncogene.
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.
Ackrill
A M
AM
Imperial Cancer Research Fund Laboratories, London, UK.
Foster
G R
GR
Laxton
C D
CD
Flavell
D M
DM
Stark
G R
GR
Kerr
I M
IM
D017456:Adenovirus Early Proteins; D000260:Adenoviruses, Human / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000502:physiology*; D005802:Genes, MHC Class II; D006367:HeLa Cells; D006801:Humans; D007370:Interferon Type I / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D007371:Interferon-gamma / Q000037:antagonists & inhibitors*; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011233:Precipitin Tests; D012330:RNA, Double-Stranded / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014162:Transfection; D014407:Tumor Cells, Cultured
D017456:Adenovirus Early Proteins; D004268:DNA-Binding Proteins; D007370:Interferon Type I; D009856:Oncogene Proteins, Viral; D012330:RNA, Double-Stranded; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma