title: A novel mechanism for the inhibition of interferon regulatory factor-3-dependent gene expression by human respiratory syncytial virus NS1 protein.
abstract: Human respiratory syncytial virus (RSV), a leading cause of respiratory tract infections in infants, inhibits type I interferon (IFN)-dependent signalling, as well as IFN synthesis. RSV non-structural protein NS1 plays a significant role in this inhibition; however, the mechanism(s) responsible is not fully known. The transcription factor interferon regulatory factor (IRF)-3 is essential for viral-induced IFN-β synthesis. In this study, we found that NS1 protein inhibits IRF-3-dependent gene transcription in constitutively active IRF-3 overexpressing cells, demonstrating that NS1 directly targets IRF-3. Our data also demonstrate that NS1 associates with IRF-3 and its transcriptional coactivator CBP, leading to disrupted association of IRF-3 to CBP and subsequent reduced binding of IRF-3 to the IFN-β promoter without blocking viral-induced IRF-3 phosphorylation, nuclear translocation and dimerization, thereby identifying a novel molecular mechanism by which RSV inhibits IFN-β synthesis.
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Junping
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Tianshuang
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Lan
authors.initials: L
authors.lastname: Pang
authors.affiliation: Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Kui
authors.initials: K
authors.lastname: Li
authors.affiliation: Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX, USA.|Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.|Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Roberto P
authors.initials: RP
authors.lastname: Garofalo
authors.affiliation: Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX, USA.|Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.|Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Antonella
authors.initials: A
authors.lastname: Casola
authors.affiliation: Department of Pediatrics, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Bao
mesh_terms: D002460:Cell Line; D004847:Epithelial Cells / Q000821:virology; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000037:antagonists & inhibitors*; D011485:Protein Binding; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D017361:Viral Nonstructural Proteins; D037521:Virulence Factors