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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism
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Animals
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DNA Primers
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Histone-Lysine N-Methyltransferase / immunology
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Histone-Lysine N-Methyltransferase / physiology*
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Humans
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Immunity, Innate
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Interferon Regulatory Factor-3 / genetics
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Interferon Regulatory Factor-3 / immunology
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Interferon Regulatory Factor-3 / metabolism*
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Intracellular Signaling Peptides and Proteins
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Mice
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Molecular Biology / methods
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NF-kappa B / genetics
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NF-kappa B / immunology
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NF-kappa B / metabolism*
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Plasmids
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Proteins / immunology
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Proteins / physiology*
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RNA, Viral / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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Toll-Like Receptors / physiology
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Transcriptional Activation
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Virus Diseases / genetics*
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Virus Diseases / immunology
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Virus Diseases / metabolism
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Viruses / genetics*
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Viruses / immunology
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Viruses / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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DNA Primers
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IRF3 protein, human
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Interferon Regulatory Factor-3
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Intracellular Signaling Peptides and Proteins
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MAVS protein, human
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NF-kappa B
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Proteins
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RNA, Viral
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Toll-Like Receptors
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WDR5 protein, human
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Wdr5 protein, mouse
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Histone-Lysine N-Methyltransferase