title: Krüppel-like factor 4 negatively regulates cellular antiviral immune response.
abstract: Viral infection triggers activation of the transcription factors NF-κB and IRF3, which collaborate to induce the expression of type I interferons (IFNs) and elicit innate antiviral response. In this report, we identified Krüppel-like factor 4 (KLF4) as a negative regulator of virus-triggered signaling. Overexpression of KLF4 inhibited virus-induced activation of ISRE and IFN-β promoter in various types of cells, while knockdown of KLF4 potentiated viral infection-triggered induction of IFNB1 and downstream genes and attenuated viral replication. In addition, KLF4 was found to be localized in the cytosol and nucleus, and viral infection promoted the translocation of KLF4 from cytosol to nucleus. Upon virus infection, KLF4 was bound to the promoter of IFNB gene and inhibited the recruitment of IRF3 to the IFNB promoter. Our study thus suggests that KLF4 negatively regulates cellular antiviral response.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Luo
authors.forename: Huan
authors.initials: H
authors.lastname: Lian
authors.forename: Bo
authors.initials: B
authors.lastname: Zhong
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Shu
authors.forename: Shu
authors.initials: S
authors.lastname: Li
mesh_terms: D002458:Cell Fractionation; D002467:Cell Nucleus / Q000276:immunology / Q000821:virology; D047369:Chromatin Immunoprecipitation; D003600:Cytosol / Q000276:immunology / Q000821:virology; D004481:Ectromelia virus / Q000254:growth & development / Q000276:immunology*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000276:immunology; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D011401:Promoter Regions, Genetic; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D029082:Sendai virus / Q000254:growth & development / Q000276:immunology*; D015398:Signal Transduction; D014779:Virus Replication
chemical_list: C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D016328:NF-kappa B; D034741:RNA, Small Interfering; D049452:Green Fluorescent Proteins; D016899:Interferon-beta; D008156:Luciferases