Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-κB and IRF3

Rashu B. Seth, Lijun Sun, Chee Kwee Ea, Zhijian J. Chen

Research output: Contribution to journalArticle

1890 Scopus citations

Abstract

Viral infection triggers host innate immune responses through activation of the transcription factors NF-κB and IRF3, which coordinately regulate the expression of type-I interferons such as interferon-β (IFN-β). Herein, we report the identification of a novel protein termed MAVS (mitochondrial antiviral signaling), which mediates the activation of NF-κB and IRF3 in response to viral infection. Silencing of MAVS expression through RNA interference abolishes the activation of NF-κB and IRF3 by viruses, thereby permitting viral replication. Conversely, overexpression of MAVS induces the expression of IFN-β through activation of NF-κB and IRF3, thus boosting antiviral immunity. Epistasis experiments show that MAVS is required for the phosphorylation of IRF3 and IκB and functions downstream of RIG-I, an intracellular receptor for viral RNA. MAVS contains an N-terminal CARD-like domain and a C-terminal transmembrane domain, both of which are essential for MAVS signaling. The transmembrane domain targets MAVS to the mitochondria, implicating a new role of mitochondria in innate immunity.

Original languageEnglish (US)
Pages (from-to)669-682
Number of pages14
JournalCell
Volume122
Issue number5
DOIs
Publication statusPublished - Sep 9 2005

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ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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