Inhibition of interferon-inducible gene expression by adenovirus E1A proteins: Block in transcriptional complex formation
- Cleveland Clinic Foundation, OH (United States)
Infection with wild-type adenovirus 5, but not with a mutant lacking the E1A gene, prevented the induction by interferon (IFN) {alpha} of chloramphenicol acetyltransferase (CAT) activity in HeLaM cell lines that had been permanently transfected with chimeric CAT reporter genes driven by the transcriptional regulatory regions of the IFN-inducible CAT activity was observed in cells that were cotransfected with the same reporter genes and plasmids expressing either the E1A 289- or 243-amino acid protein. These proteins also prevented the induction of CAT activity by IFN-{gamma} from a cotransfected HLA-DR{alpha}-CAT gene. Experiments with E1A mutants mapped the inhibitory activity to amino acid residues 38-65 of these proteins. In a HeLa cell line permanently expressing the E1A 289-amino acid protein, the replication of vesicular stomatitis virus and encephalomyocarditis virus was not inhibited by IFN-{alpha}, suggesting a global blockade of IFN responses. The observed transcriptional inhibition could be attributed to the lack of formation of the crucial IFN-stimulated gene factor 3 (ISGF3) transcriptional complex. As shown by mobility shift assays, this complex was not formed in the nuclear extracts of IFN-treated adenovirus-infected cells or IFN-treated E1A-producing cells. These nuclear extracts were deficient in both ISGF3{alpha} and ISGF3{gamma} subunits. However, they did not block the formation of ISGF3 complex from exogenously added components.
- OSTI ID:
- 5604232
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 88:17; ISSN 0027-8424; ISSN PNASA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ADENOVIRUS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMISTRY
BIOLOGICAL EFFECTS
CELL CONSTITUENTS
CHEMISTRY
DAYS LIVING RADIOISOTOPES
ENZYME INDUCTION
ENZYMES
GENE RECOMBINATION
GENE REGULATION
GROWTH FACTORS
HELA CELLS
INHIBITION
INTERFERON
ISOTOPES
LIGHT NUCLEI
LYMPHOKINES
MICROORGANISMS
MITOGENS
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
OLIGONUCLEOTIDES
ONCOGENIC VIRUSES
ORGANIC COMPOUNDS
PARASITES
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PLASMIDS
PROTEINS
RADIOISOTOPES
TRANSCRIPTION
TRANSFERASES
VIRUSES