Viral infection triggers host innate immune responses through activation of the transcription factors NF-kappaB and IRF 3, which coordinately regulate the expression of type-I interferons such as interferon-beta (IFN-beta). Herein, we report the identification of a novel protein termed MAVS (mitochondrial antiviral signaling), which mediates the activation of NF-kappaB and IRF 3 in response to viral infection. Silencing of MAVS expression through RNA interference abolishes the activation of NF-kappaB and IRF 3 by viruses, thereby permitting viral replication. Conversely, overexpression of MAVS induces the expression of IFN-beta through activation of NF-kappaB and IRF 3, thus boosting antiviral immunity. Epistasis experiments show that MAVS is required for the phosphorylation of IRF 3 and IkappaB 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.
Pubmed ID: 16125763 RIS Download
Mesh terms: Amino Acid Sequence | Animals | Cell Line | DNA-Binding Proteins | Gene Expression Regulation, Bacterial | Gene Silencing | HeLa Cells | Humans | Immunity, Innate | Interferon Regulatory Factor-3 | Interferon Regulatory Factor-7 | Interferon-beta | Interferons | Membrane Proteins | Mitochondria | Mitochondrial Proteins | Molecular Sequence Data | NF-kappa B | Protein-Serine-Threonine Kinases | RNA, Double-Stranded | Respirovirus Infections | Sendai virus | Sequence Alignment | Signal Transduction | Transcription Factors | Virus Replication
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