WDR5 is essential for assembly of the VISA-associated signaling complex and virus-triggered IRF3 and NF-kappaB activation.
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.
Wang
Yan-Yi
YY
College of Life Sciences, Modern Virology Center, Wuhan University, Wuhan 430072, China.
Liu
Li-Juan
LJ
Zhong
Bo
B
Liu
Tian-Tian
TT
Li
Ying
Y
Yang
Yan
Y
Ran
Yong
Y
Li
Shu
S
Tien
Po
P
Shu
Hong-Bing
HB
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
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