title: WDR5 is essential for assembly of the VISA-associated signaling complex and virus-triggered IRF3 and NF-kappaB activation.
abstract: Viral infection causes activation of the transcription factors NF-kappaB and IRF3, which collaborate to induce type I interferons (IFNs) and cellular antiviral response. The mitochondrial outer membrane protein VISA acts as a critical adapter for assembling a virus-induced complex that signals NF-kappaB and IRF3 activation. Using a biochemical purification approach, we identified the WD repeat protein WDR5 as a VISA-associated protein. WDR5 was recruited to VISA in a viral infection dependent manner. Viral infection also caused translocation of WDR5 from the nucleus to mitochondria. Knockdown of WDR5 impaired the formation of virus-induced VISA-associated complex. Consistently, knockdown of WDR5 inhibited virus-triggered activation of IRF3 and NF-kappaB as well as transcription of the IFNB1 gene. These findings suggest that WDR5 is essential in assembling a virus-induced VISA-associated complex and plays an important role in virus-triggered induction of type I IFNs.
authors.affiliation: College of Life Sciences, Modern Virology Center, Wuhan University, Wuhan 430072, China.
authors.forename: Yan-Yi
authors.initials: YY
authors.lastname: Wang
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Liu
authors.forename: Bo
authors.initials: B
authors.lastname: Zhong
authors.forename: Tian-Tian
authors.initials: TT
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Yong
authors.initials: Y
authors.lastname: Ran
authors.forename: Shu
authors.initials: S
authors.lastname: Li
authors.forename: Po
authors.initials: P
authors.lastname: Tien
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Shu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017931:DNA Primers; D011495:Histone-Lysine N-Methyltransferase / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008967:Molecular Biology / Q000379:methods; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010957:Plasmids; D011506:Proteins / Q000276:immunology / Q000502:physiology*; D012367:RNA, Viral / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051193:Toll-Like Receptors / Q000502:physiology; D015533:Transcriptional Activation; D014777:Virus Diseases / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D014780:Viruses / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D047908:Intracellular Signaling Peptides and Proteins; C505371:MAVS protein, human; D016328:NF-kappa B; D011506:Proteins; D012367:RNA, Viral; D051193:Toll-Like Receptors; C502547:WDR5 protein, human; C443118:Wdr5 protein, mouse; D011495:Histone-Lysine N-Methyltransferase