Proceedings of the National Academy of Sciences - PNAS, 2021-06, Vol.118 (26)
2021
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- Autor(en) / Beteiligte
- Titel
- Cellular nucleic acid-binding protein is essential for type I interferon-mediated immunity to RNA virus infection
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2021-06, Vol.118 (26)
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2021
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Type I interferons (IFNs) are innate immune cytokines required to establish cellular host defense. Precise control of IFN gene expression is crucial to maintaining immune homeostasis. Here, we demonstrated that cellular nucleic acid-binding protein (CNBP) was required for the production of type I IFNs in response to RNA virus infection. CNBP deficiency markedly impaired IFN production in macrophages and dendritic cells that were infected with a panel of RNA viruses or stimulated with synthetic double-stranded RNA. Furthermore, CNBP-deficient mice were more susceptible to influenza virus infection than were wild-type mice. Mechanistically, CNBP was phosphorylated and translocated to the nucleus, where it directly binds to the promoter of IFNb in response to RNA virus infection. Furthermore, CNBP controlled the recruitment of IFN regulatory factor (IRF) 3 and IRF7 to IFN promoters for the maximal induction of IFNb gene expression. These studies reveal a previously unrecognized role for CNBP as a transcriptional regulator of type I IFN genes engaged downstream of RNA virus-mediated innate immune signaling, which provides an additional layer of control for IRF3- and IRF7-dependent type I IFN gene expression and the antiviral innate immune response.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.2100383118Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8255963
- Format
- –
- Schlagworte
- A549 Cells, Animals, Biological Sciences, Cytokines, Dendritic cells, Double-stranded RNA, Gene expression, HEK293 Cells, Homeostasis, Humans, Immune response, Immune system, Immunity - drug effects, Infections, Influenza, Innate immunity, Interferon, Interferon regulatory factor 3, Interferon regulatory factor 7, Interferon Regulatory Factor-3 - metabolism, Interferon Regulatory Factor-7 - metabolism, Interferon Type I - metabolism, Macrophages, Mice, Mice, Inbred C57BL, Nucleic acids, Poly I-C - pharmacology, Promoter Regions, Genetic, Protein Binding - drug effects, Proteins, Ribonucleic acid, RNA, RNA Virus Infections - immunology, RNA Virus Infections - virology, RNA viruses, RNA Viruses - drug effects, RNA Viruses - immunology, RNA, Viral - metabolism, RNA-Binding Proteins - metabolism, Signal Transduction - drug effects, Transcription, Virus Replication - drug effects, Viruses, β-Interferon