TY - JOUR
T1 - Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-κB and IRF3
AU - Seth, Rashu B.
AU - Sun, Lijun
AU - Ea, Chee Kwee
AU - Chen, Zhijian J.
N1 - Funding Information:
We thank Drs. Takashi Fujita, Kate Fitzgerald, Tom Maniatis, Michael Gale, John Hiscott, and Gabriel Nunez for plasmids, and Drs. Jun-Ichiro Inoue, Wen-Chen Yeh, and Michelle Kelliher for the MEF cell lines. This work was supported by grants from NIH (RO1-AI60919), the Welch Foundation (I-1389), and the American Cancer Society (RSG0219501TBE). Confocal microscopy was supported by funding from an NIH shared instrumentation grant 1-S10-RR19406. Z.J.C. is a Leukemia and Lymphoma Society Scholar and a Burroughs Wellcome Fund Investigator in Pathogenesis of Infectious Diseases.
PY - 2005/9/9
Y1 - 2005/9/9
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cell.2005.08.012
DO - 10.1016/j.cell.2005.08.012
M3 - Article
C2 - 16125763
AN - SCOPUS:24144461689
SN - 0092-8674
VL - 122
SP - 669
EP - 682
JO - Cell
JF - Cell
IS - 5
ER -