The specific and essential role of MAVS in antiviral innate immune responses.
The mitochondrial antiviral signaling protein (MAVS) mediates the activation of NFkappaB and IRFs and the induction of interferons in response to viral infection. In vitro studies have also suggested that MAVS is required for interferon induction by cytosolic DNA, but the in vivo evidence is lacking. By generating MAVS-deficient mice, here we show that loss of MAVS abolished viral induction of interferons and prevented the activation of NFkappaB and IRF3 in multiple cell types, except plasmacytoid dendritic cells (pDCs). However, MAVS was not required for interferon induction by cytosolic DNA or by Listeria monocytogenes. Mice lacking MAVS were viable and fertile, but they failed to induce interferons in response to poly(I:C) stimulation and were severely compromised in immune defense against viral infection. These results provide the in vivo evidence that the cytosolic viral signaling pathway through MAVS is specifically required for innate immune responses against viral infection.
Sun
Qinmiao
Q
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Sun
Lijun
L
Liu
Hong-Hsing
HH
Chen
Xiang
X
Seth
Rashu B
RB
Forman
James
J
Chen
Zhijian J
ZJ
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000276:immunology*; D000818:Animals; D015139:Blotting, Southern; D015153:Blotting, Western; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D007113:Immunity, Innate; D050838:Interferon Regulatory Factor-3 / Q000276:immunology / Q000378:metabolism; D007372:Interferons / Q000276:immunology / Q000378:metabolism; D008088:Listeriosis / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008817:Mice, Mutant Strains; D024101:Mitochondrial Proteins / Q000172:deficiency / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D018353:Rhabdoviridae Infections / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; D024101:Mitochondrial Proteins; D016328:NF-kappa B; D007372:Interferons