WDR5 is essential for assembly of the VISA-associated signaling complex and virus-triggered IRF3 and NF-κB activation

Yan Yi Wang, Li Juan Liu, Bo Zhong, Tian Tian Liu, Ying Li, Yan Yang, Yong Ran, Shu Li, Po Tien, Hong Bing Shu

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

Viral infection causes activation of the transcription factors NF-κB and IRF3, which collaborate to induce type I interferons (IFNs) and cellular antiviral response.The mitochondrial outer membrane proteinVISA acts as a critical adapter for assembling a virus-induced complex that signals NF-κB and IRF3 activation. Using a biochemical purification approach, we identified the WDr epeatprotein 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-κB 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.

Original languageEnglish
Pages (from-to)815-820
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number2
DOIs
StatePublished - 2010

Keywords

  • Innate immunity
  • Interferon
  • Mitochondrial signal transduction

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