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PMID: 1614874 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Distinct activation of murine interferon-alpha promoter region by IRF-1/ISFG-2 and virus infection.

Nucleic acids research ·Vol. 20 ·No. 11 ·1992-06-11 ·Pages 2877-84

Au WC, Raj NB, Pine R, Pitha PM

Abstract

Virus infection in mouse L929 cells activates expression of interferon-alpha 4 (IFN-alpha 4), but not IFN-alpha 6. The integrity of a symmetrical sequence, GTAAAGAAAGT (alpha F1 site); (-103 to -93), present in the 35 nucleotide (nt) long inducible element (IE) (-109 to -75) of the alpha 4 promoter region is essential for the virus-induced expression. In the present study, we have shown that the interferon regulatory factor 1 (IRF-1) can induce expression of both IFN-alpha 4 and -alpha 6 in a transient expression assay. Virus infection cooperates with IRF-1 and further enhances transcription from the alpha 4 promoter, but inhibits the IRF-1-mediated expression from the alpha 6 promoter. The virus-mediated induction is determined by both IRF-1 and alpha F1 sites, while activation by IRF-1 in a cotransfection assay is not greatly influenced by the alpha F1 sequence. The activation of IFN-alpha gene promoters by IRF-1 was limited to the transient expression assay. The integrated alpha 4 promoter or the endogenous IFN-alpha genes could not be induced by transfection with IRF-1 expressing plasmid and IRF-1 did not up-regulate expression of the endogenous IRF-1 gene. However, expression of IRF-1 alone was sufficient to up-regulate the expression of two IFN stimulated genes, 2',5' oligoadenylate synthetase (OAS) and interferon stimulated (ISG)-15 gene. These results suggest that induction of IFN-alpha gene expression by virus infection requires cooperation between IRF-1 and another factor(s) that binds to the alpha F1 sequence.

MeSH Terms
2',5'-Oligoadenylate Synthetase/genetics Animals Base Sequence Binding Sites DNA-Binding Proteins/metabolism Gene Expression Gene Expression Regulation, Viral Interferon Regulatory Factor-1 Interferon-alpha/genetics L Cells Mice Molecular Sequence Data Newcastle Disease/genetics Newcastle disease virus Phosphoproteins/metabolism Polymerase Chain Reaction Promoter Regions, Genetic RNA, Messenger/genetics Regulatory Sequences, Nucleic Acid Transcription Factors/physiology
Chemicals
DNA-Binding Proteins Interferon Regulatory Factor-1 Interferon-alpha Irf1 protein, mouse Phosphoproteins RNA, Messenger Transcription Factors 2',5'-Oligoadenylate Synthetase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Au W C
Oncology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Raj N B
Pine R
Pitha P M
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
DOI
10.1093/nar/20.11.2877
Published
1992-06-11
Pages
2877-84
Language
English
Region
England
NLM ID
0411011
PMCID
PMC336936
Subset
IM
Grants
NIAID NIH HHS · AI19737 · United States
NCI NIH HHS · CA50158 · United States
External Links
PubMed source DOI: 10.1093/nar/20.11.2877 PMC Full Text View journal details
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