Abstract
The production of type I interferon is essential for viral clearance but is kept under tight control to avoid unnecessary tissue damage from hyperinflammatory responses. Here we found that OASL1 inhibited translation of IRF7, the master transcription factor for type I interferon, and thus negatively regulated the robust production of type I interferon during viral infection. OASL1 inhibited the translation of IRF7 mRNA by binding to the 5' untranslated region (UTR) of IRF7 and possibly by inhibiting scanning of the 43S preinitiation complex along the message. Oasl1-/- mice were resistant to viral infection because of the greater abundance of type I interferon, which suggests that OASL1 could be a potential therapeutic target for boosting the production of type I interferon during viral infection.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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2',5'-Oligoadenylate Synthetase / genetics
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2',5'-Oligoadenylate Synthetase / metabolism*
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5' Untranslated Regions
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Animals
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Base Sequence
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Bone Marrow Cells / immunology
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Bone Marrow Cells / metabolism
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Cell Line
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Encephalomyocarditis virus / immunology
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Gene Expression Regulation*
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Homozygote
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Humans
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Interferon Inducers / administration & dosage
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Interferon Inducers / pharmacology
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Interferon Regulatory Factor-7 / genetics*
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Interferon Regulatory Factor-7 / metabolism*
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Interferon Type I / biosynthesis
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Interferon Type I / immunology
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Macrophages / immunology
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Macrophages / metabolism
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Mice
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Mice, Knockout
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Molecular Sequence Data
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Nucleic Acid Conformation
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Poly I-C / administration & dosage
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Poly I-C / pharmacology
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Protein Binding
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Protein Biosynthesis*
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Protein Interaction Domains and Motifs
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RNA, Messenger / metabolism
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Virus Diseases / genetics
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Virus Diseases / immunology
Substances
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5' Untranslated Regions
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Interferon Inducers
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Interferon Regulatory Factor-7
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Interferon Type I
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RNA, Messenger
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Oasl1 protein, mouse
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2',5'-Oligoadenylate Synthetase
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Poly I-C