Cellular nucleic acid–binding protein is essential for type I interferon–mediated immunity to RNA virus infection
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 IF...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2021-06, Vol.118 (26), p.1-10 |
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| creator | Chen, Yongzhi Lei, Xuqiu Jiang, Zhaozhao Fitzgerald, Katherine A. |
| description | 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. |
| doi_str_mv | 10.1073/pnas.2100383118 |
| format | Article |
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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.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.2100383118</identifier><identifier>PMID: 34168080</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>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</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2021-06, Vol.118 (26), p.1-10</ispartof><rights>Copyright National Academy of Sciences Jun 29, 2021</rights><rights>2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c443t-55aef50327ace3a85f077baa3b1078d9f983235d1f3db82c56cd35e04da654793</citedby><cites>FETCH-LOGICAL-c443t-55aef50327ace3a85f077baa3b1078d9f983235d1f3db82c56cd35e04da654793</cites><orcidid>0000-0002-9768-8491 ; 0000-0002-1554-0240 ; 0000-0003-3565-6969</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/27040815$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/27040815$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34168080$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Yongzhi</creatorcontrib><creatorcontrib>Lei, Xuqiu</creatorcontrib><creatorcontrib>Jiang, Zhaozhao</creatorcontrib><creatorcontrib>Fitzgerald, Katherine A.</creatorcontrib><title>Cellular nucleic acid–binding protein is essential for type I interferon–mediated immunity to RNA virus infection</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>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.</description><subject>A549 Cells</subject><subject>Animals</subject><subject>Biological Sciences</subject><subject>Cytokines</subject><subject>Dendritic cells</subject><subject>Double-stranded RNA</subject><subject>Gene expression</subject><subject>HEK293 Cells</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunity - drug effects</subject><subject>Infections</subject><subject>Influenza</subject><subject>Innate immunity</subject><subject>Interferon</subject><subject>Interferon regulatory factor 3</subject><subject>Interferon regulatory factor 7</subject><subject>Interferon Regulatory Factor-3 - metabolism</subject><subject>Interferon Regulatory Factor-7 - metabolism</subject><subject>Interferon Type I - metabolism</subject><subject>Macrophages</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Nucleic acids</subject><subject>Poly I-C - pharmacology</subject><subject>Promoter Regions, Genetic</subject><subject>Protein Binding - drug effects</subject><subject>Proteins</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA Virus Infections - immunology</subject><subject>RNA Virus Infections - virology</subject><subject>RNA viruses</subject><subject>RNA Viruses - drug effects</subject><subject>RNA Viruses - immunology</subject><subject>RNA, Viral - metabolism</subject><subject>RNA-Binding Proteins - metabolism</subject><subject>Signal Transduction - drug effects</subject><subject>Transcription</subject><subject>Virus Replication - drug effects</subject><subject>Viruses</subject><subject>β-Interferon</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc1u1DAUhS1ERaeFNSuQpW66SXv9lzgbpGpES6UKJARry3Gc4lFiB9upNDvegTfkSfBoylBY3cX97tE59yD0msAFgYZdzl6nC0oAmGSEyGdoRaAlVc1beI5WALSpJKf8GJ2ktAGAVkh4gY4ZJ7UECSu0rO04LqOO2C9mtM5gbVz_68fPzvne-Xs8x5Ct89glbFOyPjs94iFEnLezxbfY-WzjYGPw5WiyvdPZ9thN0-Jd3uIc8OePV_jBxSUVdrAmu-BfoqNBj8m-epyn6Ov1-y_rD9Xdp5vb9dVdZThnuRJC20EAo402lmkpBmiaTmvWlfCyb4dWMspETwbWd5IaUZueCQu817XgTctO0bu97rx0xZsp9qMe1RzdpONWBe3Uvxvvvqn78KAkFaKtWRE4fxSI4ftiU1aTS6a8THsblqSo4KIupkRT0LP_0E1Yoi_xdlTb0JrKnaPLPWViSCna4WCGgNpVqnaVqr-Vlou3TzMc-D8dFuDNHtikHOJhTxvgIIlgvwHqRqrq</recordid><startdate>20210629</startdate><enddate>20210629</enddate><creator>Chen, Yongzhi</creator><creator>Lei, Xuqiu</creator><creator>Jiang, Zhaozhao</creator><creator>Fitzgerald, Katherine A.</creator><general>National Academy of Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-9768-8491</orcidid><orcidid>https://orcid.org/0000-0002-1554-0240</orcidid><orcidid>https://orcid.org/0000-0003-3565-6969</orcidid></search><sort><creationdate>20210629</creationdate><title>Cellular nucleic acid–binding protein is essential for type I interferon–mediated immunity to RNA virus infection</title><author>Chen, Yongzhi ; Lei, Xuqiu ; Jiang, Zhaozhao ; Fitzgerald, Katherine A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c443t-55aef50327ace3a85f077baa3b1078d9f983235d1f3db82c56cd35e04da654793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>A549 Cells</topic><topic>Animals</topic><topic>Biological Sciences</topic><topic>Cytokines</topic><topic>Dendritic cells</topic><topic>Double-stranded RNA</topic><topic>Gene expression</topic><topic>HEK293 Cells</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immune system</topic><topic>Immunity - drug effects</topic><topic>Infections</topic><topic>Influenza</topic><topic>Innate immunity</topic><topic>Interferon</topic><topic>Interferon regulatory factor 3</topic><topic>Interferon regulatory factor 7</topic><topic>Interferon Regulatory Factor-3 - metabolism</topic><topic>Interferon Regulatory Factor-7 - metabolism</topic><topic>Interferon Type I - metabolism</topic><topic>Macrophages</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Nucleic acids</topic><topic>Poly I-C - pharmacology</topic><topic>Promoter Regions, Genetic</topic><topic>Protein Binding - drug effects</topic><topic>Proteins</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA Virus Infections - immunology</topic><topic>RNA Virus Infections - virology</topic><topic>RNA viruses</topic><topic>RNA Viruses - drug effects</topic><topic>RNA Viruses - immunology</topic><topic>RNA, Viral - metabolism</topic><topic>RNA-Binding Proteins - metabolism</topic><topic>Signal Transduction - drug effects</topic><topic>Transcription</topic><topic>Virus Replication - drug effects</topic><topic>Viruses</topic><topic>β-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Yongzhi</creatorcontrib><creatorcontrib>Lei, Xuqiu</creatorcontrib><creatorcontrib>Jiang, Zhaozhao</creatorcontrib><creatorcontrib>Fitzgerald, Katherine A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Yongzhi</au><au>Lei, Xuqiu</au><au>Jiang, Zhaozhao</au><au>Fitzgerald, Katherine A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cellular nucleic acid–binding protein is essential for type I interferon–mediated immunity to RNA virus infection</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2021-06-29</date><risdate>2021</risdate><volume>118</volume><issue>26</issue><spage>1</spage><epage>10</epage><pages>1-10</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>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.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>34168080</pmid><doi>10.1073/pnas.2100383118</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-9768-8491</orcidid><orcidid>https://orcid.org/0000-0002-1554-0240</orcidid><orcidid>https://orcid.org/0000-0003-3565-6969</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 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 |
| title | Cellular nucleic acid–binding protein is essential for type I interferon–mediated immunity to RNA virus infection |
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