Identification and Characterization of MAVS, a Mitochondrial Antiviral Signaling Protein that Activates NF-κB and IRF3

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

doi:10.1016/j.cell.2005.08.012

Cited by 3,329interferon and immune responsesImmune Response and InflammationNF-κB Signaling Pathways

Identification and Characterization of MAVS, a Mitochondrial Antiviral Signaling Protein that Activates NF-κB and IRF3

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Seth, Rashu B., Sun, Lijun, Ea, Chee-Kwee, Chen, Zhijian J.·2005·Cell

DOI 10.1016/j.cell.2005.08.012

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Abstract

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.

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MAVS localization to the outer mitochondrial membrane is indispensable for its function in RLR signaling.
“A breakthrough in establishing the role for mitochondria in RLR-activated antiviral immunity was the identification of the RLR mitochondrial adaptor protein MAVS (mitochondrial antiviral-signaling protein)(Kawai et al., 2005; Meylan et al., 2005; Seth et al., 2005; Xu et al., 2005) localization to the outer mitochondrial membrane is indispensable for its function.”
From Mitochondria in the Regulation of Innate and Adaptive Immunity (2015) · cites this paper as Seth et al., 2005

Toll-like receptor signalling
Akira, S., & Takeda, K. (2004) · Nature reviews. Immunology · doi:10.1038/nri1391 · Cited by 8,312 · see citing works
Jak-STAT Pathways and Transcriptional Activation in Response to IFNs and Other Extracellular Signaling Proteins
Darnell, J. E., Kerr, L. M., & Stark, G. R. (1994) · Science · doi:10.1126/science.8197455 · Cited by 6,080 · cited 1× · see citing works
“These interferons activate the JAK-STAT pathway to stimulate the expression of interferon-stimulated genes (ISGs), which collectively inhibit viral replication and assembly (Darnell et al., 1994).”
The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses
Yoneyama, M., Kikuchi, M., Natsukawa, T., Shinobu, N., Imaizumi, T., Miyagishi, M., Taira, K., Akira, S., & Fujita, T. (2004) · Nature Immunology · doi:10.1038/ni1087 · Cited by 3,935 · see citing works
Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death
Hockenbery, D., Nuñez, G., Milliman, C., Schreiber, R. D., & Korsmeyer, S. J. (1990) · Nature · doi:10.1038/348334a0 · Cited by 3,720 · see citing works
IKKε and TBK1 are essential components of the IRF3 signaling pathway
Fitzgerald, K. A., McWhirter, S. M., Faia, K. L., Rowe, D. C., Latz, E., Golenbock, D. T., Coyle, A. J., Liao, S.-M., & Maniatis, T. (2003) · Nature Immunology · doi:10.1038/ni921 · Cited by 2,680 · see citing works
Untitled work
(2001) · PubMed · Cited by 2,381 · see citing works
IRF-7 is the master regulator of type-I interferon-dependent immune responses
Honda, K., Yanai, H., Negishi, H., Asagiri, M., Sato, M., Mizutani, T., Shimada, N., Ohba, Y., Takaoka, A., Yoshida, N., et al. (2005) · Nature · doi:10.1038/nature03464 · Cited by 2,229 · see citing works
Activation of the IκB Kinase Complex by TRAF6 Requires a Dimeric Ubiquitin-Conjugating Enzyme Complex and a Unique Polyubiquitin Chain
Deng, L., Wang, C., Spencer, E., Yang, L., Braun, A., You, J., Slaughter, C., Pickart, C., & Chen, Z. J. (2000) · Cell · doi:10.1016/s0092-8674(00)00126-4 · Cited by 1,872 · see citing works
Self-citation
Triggering the Interferon Antiviral Response Through an IKK-Related Pathway
Sharma, S., tenOever, B. R., Grandvaux, N., Zhou, G., Lin, R., & Hiscott, J. B. (2003) · Science · doi:10.1126/science.1081315 · Cited by 1,664 · see citing works
Immunology of hepatitis B virus and hepatitis C virus infection
Rehermann, B., & Nascimbeni, M. (2005) · Nature reviews. Immunology · doi:10.1038/nri1573 · Cited by 1,618 · see citing works
Cell Type-Specific Involvement of RIG-I in Antiviral Response
Kato, H., Sato, S., Yoneyama, M., Yamamoto, M., Uematsu, S., Matsui, K., Tsujimura, T., Takeda, K., Fujita, T., Takeuchi, O., et al. (2005) · Immunity · doi:10.1016/j.immuni.2005.04.010 · Cited by 1,368 · see citing works
Activation of DNA-binding activity in an apparently cytoplasmic precursor of the NF-κB transcription factor
Baeuerle, P. A., & Baltimore, D. (1988) · Cell · doi:10.1016/0092-8674(88)90382-0 · Cited by 1,166 · see citing works
Interferon-α induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6
Kawai, T., Sato, S., Ishii, K. J., Coban, C., Hemmi, H., Yamamoto, M., Terai, K., Matsuda, M., Inoue, J., Uematsu, S., et al. (2004) · Nature Immunology · doi:10.1038/ni1118 · Cited by 1,038 · see citing works
The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN -β promoter
Andrejeva, J., Childs, K., Young, D. F., Carlos, T. S., Stock, N., Goodbourn, S., & Randall, R. E. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407639101 · Cited by 990 · see citing works
NF-κB signaling pathways in mammalian and insect innate immunityPreprint
Silverman, N. S., & Maniatis, T. (2001) · Genes & Development · doi:10.1101/gad.909001 · Cited by 904 · see citing works
Regulating Intracellular Antiviral Defense and Permissiveness to Hepatitis C Virus RNA Replication through a Cellular RNA Helicase, RIG-I
Sumpter, R., Loo, Y., Foy, E. M., Li, K., Yoneyama, M., Fujita, T., Lemon, S. M., & Gale, M. (2005) · Journal of Virology · doi:10.1128/jvi.79.5.2689-2699.2005 · Cited by 900 · see citing works
Differential Localization of Rho Gtpases in Live Cells
Michaelson, D., Silletti, J., Murphy, G., D'Eustachio, P., Rush, M., & Philips, M. R. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.152.1.111 · Cited by 679 · see citing works
Distinct molecular mechanism for initiating TRAF6 signalling
Ye, H., Arron, J. R., Lamothe, B., Cirilli, M., Kobayashi, T., Shevde, N. K., Segal, D., Dzivenu, O. K., Vologodskaia, M., Yim, M., et al. (2002) · Nature · doi:10.1038/nature00888 · Cited by 665 · see citing works
mda-5 : An interferon-inducible putative RNA helicase with double-stranded RNA-dependent ATPase activity and melanoma growth-suppressive properties
Kang, D.-C., Gopalkrishnan, R. V., Wu, Q., Jankowsky, E., Pyle, A. M., & Fisher, P. B. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.022637199 · Cited by 651 · see citing works
The Roles of Two IκB Kinase-related Kinases in Lipopolysaccharide and Double Stranded RNA Signaling and Viral Infection
Hemmi, H., Takeuchi, O., Sato, S., Yamamoto, M., Kaisho, T., Sanjo, H., Kawai, T., Hoshino, K., Takeda, K., & Akira, S. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20040520 · Cited by 576 · see citing works
IFN-regulatory factor 3-dependent gene expression is defective in Tbk1 -deficient mouse embryonic fibroblasts
McWhirter, S. M., Fitzgerald, K. A., Rosains, J., Rowe, D. C., Golenbock, D. T., & Maniatis, T. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2237236100 · Cited by 540 · see citing works
The novel functions of ubiquitination in signaling
Sun, L., & Chen, Z. J. (2004) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2004.02.005 · Cited by 465 · see citing works
Self-citation
Differential Requirement for TANK-binding Kinase-1 in Type I Interferon Responses to Toll-like Receptor Activation and Viral Infection
Perry, A. K., Chow, E. K., Goodnough, J. B., Yeh, W., & Cheng, G. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20040528 · Cited by 399 · see citing works
Large-scale identification and characterization of human genes that activate NF-κB and MAPK signaling pathways
Matsuda, A., Suzuki, Y., Honda, G., Muramatsu, S., Matsuzaki, O., Nagano, Y., Doi, T., Shimotohno, K., Harada, T., Nishida, E., et al. (2003) · Oncogene · doi:10.1038/sj.onc.1206406 · Cited by 395 · see citing works
Structure and Function of the Interferon- EnhanceosomePreprint
Maniatis, T., Falvo, J. V., Kim, T. H., KIM, T. K., Lin, C. H., Parekh, B., & WATHELET, M. G. (1998) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1998.63.609 · Cited by 358 · see citing works
Characterization of the signal that directs Bcl-xL, but not Bcl-2, to the mitochondrial outer membrane
Kaufmann, T., Schlipf, S., Sanz, J., Neubert, K., Stein, R., & Borner, C. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200210084 · Cited by 345 · see citing works
Cutting Edge: TNFR-Associated Factor (TRAF) 6 Is Essential for MyD88-Dependent Pathway but Not Toll/IL-1 Receptor Domain-Containing Adaptor-Inducing IFN-β (TRIF)-Dependent Pathway in TLR Signaling
Gohda, J., Matsumura, T., & Inoue, J. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.5.2913 · Cited by 312 · see citing works
A FADD-dependent innate immune mechanism in mammalian cells
Balachandran, S., Thomas, E., & Barber, G. N. (2004) · Nature · doi:10.1038/nature03124 · Cited by 294 · see citing works
RICK, a Novel Protein Kinase Containing a Caspase Recruitment Domain, Interacts with CLARP and Regulates CD95-mediated Apoptosis
Inohara, N., del Peso, L., Koseki, T., Chen, S., & Núñez, G. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.20.12296 · Cited by 245 · see citing works
Activation of TBK1 and IKKε Kinases by Vesicular Stomatitis Virus Infection and the Role of Viral Ribonucleoprotein in the Development of Interferon Antiviral Immunity
tenOever, B. R., Sharma, S., Zou, W., Sun, Q., Grandvaux, N., Julkunen, I., Hemmi, H., Yamamoto, M., Akira, S., Yeh, W., et al. (2004) · Journal of Virology · doi:10.1128/jvi.78.19.10636-10649.2004 · Cited by 181 · see citing works
Targeting of Hepatitis C Virus Core Protein to Mitochondria through a Novel C-Terminal Localization Motif
Schwer, B., Ren, S., Pietschmann, T., Kartenbeck, J., Kaehlcke, K., Bartenschlager, R. F. W., Yen, T. S. B., & Ott, M. (2004) · Journal of Virology · doi:10.1128/jvi.78.15.7958-7968.2004 · Cited by 171 · see citing works
TLR7: A new sensor of viral infection
Crozat, K., & Beutler, B. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401347101 · Cited by 163 · see citing works
IFN-regulatory factor 3-dependent gene expression is defective in Tbk1-deficient mouse embryonic fibroblasts
Kopp, E. B. (2004) · Medical Entomology and Zoology · Cited by 160 · see citing works
Review: Control of IRF-3 Activation by Phosphorylation
Yoneyama, M., Suhara, W., & Fujita, T. (2002) · Journal of Interferon & Cytokine Research · doi:10.1089/107999002753452674 · Cited by 158 · see citing works
Overexpression of Helicard, a CARD-Containing Helicase Cleaved during Apoptosis, Accelerates DNA Degradation
Kovacsovics, M., Martinon, F., Micheau, O., Bodmer, J.-L., Hofmann, K., & Tschopp, J. (2002) · Current Biology · doi:10.1016/s0960-9822(02)00842-4 · Cited by 136 · see citing works
Convergence of the NF‐κB and Interferon Signaling Pathways in the Regulation of Antiviral Defense and Apoptosis
Hiscott, J. B., Grandvaux, N., Sharma, S., tenOever, B. R., Servant, M. J., & Lin, R. (2003) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1299.042 · Cited by 107 · see citing works
Identification of the Endoplasmic Reticulum Targeting Signal in Vesicle-associated Membrane Proteins
Kim, P. K., Hollerbach, C., Trimble, W. S., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.52.36876 · Cited by 52 · see citing works
Kinasing and Clipping Down the NF-κB Trail
van Oers, N. S. C., & Chen, Z. J. (2005) · Science · doi:10.1126/science.1110902 · Cited by 31 · see citing works
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Guo (2020) · doi:10.1186/s40779-020-00240-0 · Cited by 4,735 · see citing works
Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses
Kato, H., Takeuchi, O., Sato, S., Yoneyama, M., Yamamoto, M., Matsui, K., Uematsu, S., Jung, A., Kawai, T., Ishii, K. J., et al. (2006) · Nature · doi:10.1038/nature04734 · Cited by 3,888 · see citing works
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Ishikawa, H., & Barber, G. N. (2008) · Nature · doi:10.1038/nature07317 · Cited by 3,576 · see citing works
Interferon-stimulated genes: A complex web of host defenses
Schneider, W. M., Chevillotte, M. D., & Rice, C. M. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120231 · Cited by 3,067 · see citing works
STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity
Ishikawa, H., Ma, Z., & Barber, G. N. (2009) · Nature · doi:10.1038/nature08476 · Cited by 2,759 · see citing works
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Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus
Meylan, E., Curran, J., Hofmann, K., Moradpour, D., Binder, M., Bartenschlager, R., & Tschopp, J. (2005) · Nature · doi:10.1038/nature04193 · Cited by 2,401 · see citing works
Mitochondria: More Than Just a Powerhouse
McBride, H. M., Neuspiel, M., & Wasiak, S. (2006) · Current Biology · doi:10.1016/j.cub.2006.06.054 · Cited by 1,985 · see citing works
Innate immune recognition of viral infection
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Roulois, D., Loo Yau, H., Singhania, R., Wang, Y., Danesh, A., Shen, S. Y., Han, H., Liang, G., Jones, P. A., Pugh, T. J., et al. (2015) · Cell · doi:10.1016/j.cell.2015.07.056 · Cited by 1,527 · see citing works
The mitochondrial basis of aging
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The IRF Family Transcription Factors in Immunity and Oncogenesis
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Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases
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Loo, Y.-M., Fornek, J., Crochet, N., Bajwa, G., Perwitasari, O., Martinez-Sobrido, L., Akira, S., Gill, M. A., García-Sastre, A., Katze, M. G., et al. (2008) · Journal of Virology · doi:10.1128/jvi.01080-07 · Cited by 1,071 · see citing works
Mitochondrial Dynamics in Mammalian Health and Disease
Liesa, M., Palacín, M., & Zorzano, A. (2009) · Physiological Reviews · doi:10.1152/physrev.00030.2008 · Cited by 953 · see citing works
Mitochondria in the Regulation of Innate and Adaptive Immunity
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Activation and evasion of type I interferon responses by SARS-CoV-2
Lei, X., Dong, X., Ma, R., Wang, W., Xiao, X., Tian, Z., Wang, C., Wang, Y., Li, L., Ren, L., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17665-9 · Cited by 980 · see citing works
Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses
Alameh, M.-G., Tombácz, I., Bettini, E., Lederer, K., Ndeupen, S., Sittplangkoon, C., Wilmore, J. R., Gaudette, B. T., Soliman, O. Y., Pine, M., et al. (2021) · Immunity · doi:10.1016/j.immuni.2021.11.001 · Cited by 775 · see citing works
MicroRNA-146a Feedback Inhibits RIG-I-Dependent Type I IFN Production in Macrophages by Targeting TRAF6, IRAK1, and IRAK2
Hou, J., Wang, P., Lin, L., Liu, X., Ma, F., An, H., Wang, Z., & Cao, X. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0900707 · Cited by 739 · see citing works
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Yun, J., & Finkel, T. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.01.011 · Cited by 626 · see citing works
Sensing of RNA viruses: a review of innate immune receptors involved in recognizing RNA virus invasion
Jensen, S., & Thomsen, A. R. (2012) · Journal of Virology · doi:10.1128/jvi.05738-11 · Cited by 604 · see citing works
RIG-I detects viral genomic RNA during negative-strand RNA virus infection
Rehwinkel, J., Tan, C. P., Goubau, D., Schulz, O., Pichlmair, A., Bier, K., Robb, N., Vreede, F., Barclay, W., Fodor, E., et al. (2010) · Cell · doi:10.1016/j.cell.2010.01.020 · Cited by 585 · see citing works
Nucleic acid recognition by the innate immune system
Barbalat, R., Ewald, S. E., Mouchess, M. L., & Barton, G. M. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101340 · Cited by 577 · see citing works
Mitochondria as signaling organelles
Chandel, N. S. (2014) · BMC Biology · doi:10.1186/1741-7007-12-34 · Cited by 576 · see citing works
The role of mitochondria in NLRP3 inflammasome activation
Liu, Q., Zhang, D., Hu, D., Zhou, X., & Zhou, Y. (2018) · Molecular Immunology · doi:10.1016/j.molimm.2018.09.010 · Cited by 475 · see citing works
Mitochondria and cell signalling
Tait, S. W. G., & Green, D. R. (2012) · Journal of Cell Science · doi:10.1242/jcs.099234 · Cited by 453 · see citing works
Regulation of IRF-3-dependent Innate Immunity by the Papain-like Protease Domain of the Severe Acute Respiratory Syndrome Coronavirus
Devaraj, S. G., Wang, N., Chen, Z., Chen, Z., Tseng, M., Barretto, N., Lin, R., Peters, C. J., Tseng, C.-T. K., Baker, S. C., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704870200 · Cited by 411 · see citing works
Self-citation
Mitochondria in innate immune signaling
Banoth, B., & Cassel, S. L. (2018) · Translational Research · doi:10.1016/j.trsl.2018.07.014 · Cited by 410 · see citing works
Mitochondria: diversity in the regulation of the NLRP3 inflammasome
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Resurrection of endogenous retroviruses during aging reinforces senescence
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Self-citation
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The Peroxisome-Mitochondria Connection: How and Why?
Fransen, M., Lismont, C., & Walton, P. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18061126 · Cited by 351 · see citing works
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Holley, A. K., Bakthavatchalu, V., Velez-Roman, J. M., & St. Clair, D. K. (2011) · International Journal of Molecular Sciences · doi:10.3390/ijms12107114 · Cited by 358 · see citing works
Host-cell sensors for Plasmodium activate innate immunity against liver-stage infection
Liehl, P., Zuzarte-Luís, V., Chan, J., Zillinger, T., Baptista, F., Carapau, D., Konert, M., Hanson, K. K., Carret, C., Lassnig, C., et al. (2014) · Nature Medicine · doi:10.1038/nm.3424 · Cited by 313 · see citing works
Nuclear sensing of breaks in mitochondrial DNA enhances immune surveillance
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Mitochondrial dynamics regulate the RIG-I-like receptor antiviral pathway
Castanier, C., Garcin, D., Vazquez, A., & Arnoult, D. (2010) · The EMBO Reports · doi:10.1038/embor.2009.258 · Cited by 316 · see citing works
PGAM5 tethers a ternary complex containing Keap1 and Nrf2 to mitochondria
Lo, S.-C., & Hannink, M. (2008) · Experimental Cell Research · doi:10.1016/j.yexcr.2008.02.014 · Cited by 300 · see citing works
Nlrp6 regulates intestinal antiviral innate immunity
Wang, P., Zhu, S., Yang, L., Cui, S., Pan, W., Jackson, R., Zheng, Y., Rongvaux, A., Sun, Q., Yang, G., et al. (2015) · Science · doi:10.1126/science.aab3145 · Cited by 304 · see citing works
The function and clinical application of extracellular vesicles in innate immune regulation
Zhou, X., Xie, F., Wang, L., Zhang, L., Zhang, S., Fang, M., & Zhou, F. (2020) · Cellular & Molecular Immunology · doi:10.1038/s41423-020-0391-1 · Cited by 294 · see citing works
Nrf2 negatively regulates STING indicating a link between antiviral sensing and metabolic reprogramming
Olagnier, D., Brandtoft, A. M., Gunderstofte, C., Villadsen, N. L., Krapp, C., Thielke, A. L., Laustsen, A., Peri, S., Hansen, A. L., Bonefeld, L., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05861-7 · Cited by 282 · see citing works
Regulation of hepatic innate immunity by hepatitis C virus
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The genetic basis of parental care evolution in monogamous mice
Bendesky, A., Kwon, Y.-M., Lassance, J.-M., Lewarch, C. L., Yao, S., Peterson, B. K., He, M. X., Dulac, C., & Hoekstra, H. E. (2017) · Nature · doi:10.1038/nature22074 · Cited by 268 · see citing works
Mitofusin 2 Inhibits Mitochondrial Antiviral Signaling
Yasukawa, K., Oshiumi, H., Takeda, M., Ishihara, N., Yanagi, Y., Seya, T., Kawabata, S.-I., & Koshiba, T. (2009) · Science Signaling · doi:10.1126/scisignal.2000287 · Cited by 255 · see citing works
Pathogen recognition by innate immunity and its signaling
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Human Cytomegalovirus Tegument Protein pUL83 Inhibits IFI16-Mediated DNA Sensing for Immune Evasion
Li, T., Chen, J., & Cristea, I. M. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2013.10.007 · Cited by 226 · see citing works
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Guo, L., Tian, J., & Du, H. (2017) · Journal of Alzheimer’s Disease · doi:10.3233/jad-160702 · Cited by 211 · see citing works
Linear Ubiquitin Assembly Complex Negatively Regulates RIG-I- and TRIM25-Mediated Type I Interferon Induction
Inn, K.-S., Gack, M. U., Tokunaga, F., Shi, M., Wong, L.-Y., Iwai, K., & Jung, J. U. (2011) · Molecular Cell · doi:10.1016/j.molcel.2010.12.029 · Cited by 209 · see citing works
Interferons: Signaling, antiviral and viral evasion
Bonjardim, C. A., Ferreira, P. C. P., & Kroon, E. G. (2009) · Immunology Letters · doi:10.1016/j.imlet.2008.11.002 · Cited by 196 · see citing works
IRF family proteins and type I interferon induction in dendritic cells
Tailor, P., Tamura, T., & Ozato, K. (2006) · Cell Research · doi:10.1038/sj.cr.7310018 · Cited by 186 · see citing works
Mitochondrial control of the NLRP3 inflammasome
Kepp, O., Galluzzi, L., & Kroemer, G. (2011) · Nature Immunology · doi:10.1038/ni0311-199 · Cited by 168 · see citing works
p53 engages the cGAS/STING cytosolic DNA sensing pathway for tumor suppression
Ghosh, M., Saha, S., Li, J., Montrose, D. C., & Martinez, L. A. (2023) · Molecular Cell · doi:10.1016/j.molcel.2022.12.023 · Cited by 166 · see citing works
Genomic instability, inflammatory signaling and response to cancer immunotherapy
Chen, M., Linstra, R., & van Vugt, M. A. T. M. (2022) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2021.188661 · Cited by 166 · see citing works
The proinflammatory cytokine-induced IRG1 protein associates with mitochondria
Degrandi, D., Hoffmann, R., Beuter-Gunia, C., & Pfeffer, K. (2009) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2008.0013 · Cited by 155 · see citing works
Mitochondria Restrict Growth of the Intracellular Parasite Toxoplasma gondii by Limiting Its Uptake of Fatty Acids
Pernas, L., Bean, C., Boothroyd, J. C., & Scorrano, L. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.02.018 · Cited by 144 · see citing works
Mitochondria as a centrally positioned hub in the innate immune response
Sandhir, R., Halder, A., & Sunkaria, A. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.10.020 · Cited by 135 · see citing works
COX5B regulates MAVS-mediated antiviral signaling through interaction with ATG5 and repressing ROS production
Zhao, Y., Sun, X., Nie, X., Sun, L., Tang, T.-S., Chen, D., & Sun, Q. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1003086 · Cited by 129 · see citing works
Brain immune cells undergo cGAS/STING-dependent apoptosis during herpes simplex virus type 1 infection to limit type I IFN production
Reinert, L. S., Rashidi, A. S., Tran, D. N., Katzilieris-Petras, G., Hvidt, A. K., Gohr, M., Fruhwürth, S., Bodda, C., Thomsen, M. K., Vendelbo, M. H., et al. (2021) · Journal of Clinical Investigation · doi:10.1172/jci136824 · Cited by 118 · see citing works
LINE1 contributes to autoimmunity through both RIG-I- and MDA5-mediated RNA sensing pathways
Zhao, K., Du, J., Peng, Y., Li, P., Wang, S., Wang, Y., Hou, J., Kang, J., Zheng, W., Hua, S., et al. (2018) · Journal of Autoimmunity · doi:10.1016/j.jaut.2018.02.007 · Cited by 106 · see citing works
Cytoplasmic Mechanisms of Recognition and Defense of Microbial Nucleic Acids
Hu, M.-M., & Shu, H.-B. (2018) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100617-062903 · Cited by 110 · see citing works
TBK1, a central kinase in innate immune sensing of nucleic acids and beyond
Zhou, R., Zhang, Q., & Xu, P. (2020) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmaa051 · Cited by 104 · see citing works
Convergent evolution of escape from hepaciviral antagonism in primates
Patel, M. R., Loo, Y.-M., Horner, S. M., Gale, M., & Malik, H. S. (2012) · PLoS Biology · doi:10.1371/journal.pbio.1001282 · Cited by 95 · see citing works
Candida pathogens induce protective mitochondria-associated type I interferon signalling and a damage-driven response in vaginal epithelial cells
Pekmezovic, M., Hovhannisyan, H., Gresnigt, M. S., Iracane, E., Oliveira-Pacheco, J., Siscar-Lewin, S., Seemann, E., Qualmann, B., Kalkreuter, T., Müller, S., et al. (2021) · Nature Microbiology · doi:10.1038/s41564-021-00875-2 · Cited by 96 · see citing works
An Essential Role for RIG-I in Toll-like Receptor-Stimulated Phagocytosis
Kong, L., Sun, L., Zhang, H., Liu, Q., Liu, Y., Qin, L., Shi, G., Hu, J.-H., Xu, A., Sun, Y.-P., et al. (2009) · Cell Host & Microbe · doi:10.1016/j.chom.2009.06.008 · Cited by 86 · see citing works
Self-citation
Powering the Immune System: Mitochondria in Immune Function and Deficiency
Walker, M. A., Volpi, S., Sims, K. B., Walter, J. E., & Traggiai, E. (2014) · Journal of Immunology Research · doi:10.1155/2014/164309 · Cited by 83 · see citing works
PNPASE and RNA trafficking into mitochondria
Wang, G., Shimada, E., Koehler, C. M., & Teitell, M. A. (2012) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2011.10.001 · Cited by 84 · see citing works
FLN29 Deficiency Reveals Its Negative Regulatory Role in the Toll-like Receptor (TLR) and Retinoic Acid-inducible Gene I (RIG-I)-like Helicase Signaling Pathway
Sanada, T., Takaesu, G., Mashima, R., Yoshida, R., Kobayashi, T., & Yoshimura, A. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m806923200 · Cited by 66 · see citing works
Cell deaths: Involvement in the pathogenesis and intervention therapy of COVID-19
Li, X., Zhang, Z., Wang, Z., Gutiérrez-Castrellón, P., & Shi, H. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01043-6 · Cited by 67 · see citing works
TANK-binding kinase 1 as a novel therapeutic target for viral diseases
Zhao, C., & Zhao, W. (2019) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2019.1601702 · Cited by 61 · see citing works
Retinoic Acid-induced Gene-1 (RIG-I) Associates with the Actin Cytoskeleton via Caspase Activation and Recruitment Domain-dependent Interactions
Mukherjee, A., Morosky, S. A., Shen, L., Weber, C. R., Turner, J. R., Kim, K. S., Wang, T., & Coyne, C. B. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m807547200 · Cited by 62 · see citing works
Structure-Function Analysis of the Yeast Mitochondrial Rho GTPase, Gem1p
Koshiba, T., Holman, H. A., Kubara, K., Yasukawa, K., Kawabata, S.-I., Okamoto, K., Macfarlane, J., & Shaw, J. M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.180034 · Cited by 50 · see citing works
Novel insights into stress-induced susceptibility to influenza: corticosterone impacts interferon-β responses by Mfn2-mediated ubiquitin degradation of MAVS
Luo, Z., Liu, L.-F., Jiang, Y.-N., Tang, L.-P., Li, W., Ouyang, S.-H., Tu, L.-F., Wu, Y.-P., Gong, H.-B., Yan, C.-Y., et al. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00238-z · Cited by 34 · see citing works
“Stress/CORT impeded MAVS antiviral signaling MAVS can potently activate IRF3 and propagate IFNs and ISGs, which plays a crucial role in defending RNA virus infection.(20,21) We thus investigated the effect of stress/CORT on MAVS antiviral signaling pathway.”
Background
An IMiD-induced SALL4 degron system for selective degradation of target proteins
Yamanaka, S., Shoya, Y., Matsuoka, S., Nishida-Fukuda, H., Shibata, N., & Sawasaki, T. (2020) · Communications Biology · doi:10.1038/s42003-020-01240-5 · Cited by 29 · see citing works
Aspects of innate immunity and Parkinson's disease
Huang, Y., & Halliday, G. M. (2012) · Frontiers in Pharmacology · doi:10.3389/fphar.2012.00033 · Cited by 22 · see citing works
VISA—A pass to innate immunity
Qi, B., Huang, Y., Rowe, D., & Halliday, G. (2007) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2006.08.016 · Cited by 18 · see citing works
Dampening of ISGylation of RIG-I by ADAP regulates type I interferon response of macrophages to RNA virus infection
Wang, Y., Feng, H., Li, X., Ruan, Y., Guo, Y., Cui, X., Zhang, P., Li, Y., Wang, X., Wang, X., et al. (2024) · PLOS Pathogens · doi:10.1371/journal.ppat.1012230 · Cited by 7 · see citing works
Exploring the Genetic Origin of Brazilian Locally Adapted Breeds: Admixture, Population History and Relationship with Portuguese and Indicine Cattle
Verardo, L. L., Otto, P. I., Machado, M. A., do Carmo Panetto, J. C., Faza, D. R. D. L. R., Alves do Egito, A., Vitorino, A. S. M., Carolino, M. I. C. M., Carolino, N. P., & da Silva, M. V. G. B. (2024) · Livestock Science · doi:10.1016/j.livsci.2024.105455 · Cited by 3 · see citing works

Grass Carp Reovirus Nonstructural Proteins Avoid Host Antiviral Immune Response by Targeting the RLR Signaling Pathway
Zhang, J., Wu, X. M., Fang, Q., et al. (2022) · The Journal of Immunology · doi:10.4049/jimmunol.2100723 · Cited by 32 · see citing works
Interferon-regulatory factors, IRF3 and IRF7 in Asian seabass, Lates calcarifer: Characterization, ontogeny and transcriptional modulation upon challenge with nervous necrosis virus
Krishnan, R., Kurcheti, P. P., Mushtaq, Z., Jeena, K., & Vismai Naik, T. (2019) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2019.03.073 · Cited by 36 · see citing works
Adaptations of Interferon Regulatory Factor 3 with Transition from Terrestrial to Aquatic Life
Angeletti, M., Hsu, W.-L. N., Majo, N., Moriyama, H., Moriyama, E. N., & Zhang, L. (2020) · Scientific Reports · doi:10.1038/s41598-020-61365-9 · Cited by 21 · see citing works
Transcriptional and Non-Transcriptional Activation, Posttranslational Modifications, and Antiviral Functions of Interferon Regulatory Factor 3 and Viral Antagonism by the SARS-Coronavirus
Glanz, A., Chakravarty, S., Varghese, M., Kottapalli, A., Fan, S., Chakravarti, R., & Chattopadhyay, S. (2021) · Viruses · doi:10.3390/v13040575 · Cited by 42 · see citing works
ELF4 is critical for induction of type I interferon and the host antiviral response
You, F., Wang, P., Yang, L., Yang, G., Zhao, Y. O., Qian, F., Walker, W. E., Sutton, R. E., Montgomery, R. R., Lin, R., et al. (2013) · Nature Immunology · doi:10.1038/ni.2756 · Cited by 121 · see citing works

Authors: Seth, R. B., Sun, L., Ea, C.-K., & Chen, Z. J.
Affiliations: Howard Hughes Medical Institute (US)
Corresponding author: Chen, Zhijian J.
ORCID: Sun, Lijun
Ea, Chee-Kwee
Chen, Zhijian J.
Venue: Cell
Publisher: Elsevier BV
Published: 2005-09
Volume: 122
Issue: 5
Pages: 669-682
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2005.08.012
OpenAlex: W2107513655
Cited by: 3,329
References: 38
Citations by year: 2026: 145 · 2025: 162 · 2024: 165 · 2023: 174 · 2022: 173 · 2021: 221 · 2020: 212 · 2019: 166 · 2018: 168 · 2017: 153 · 2016: 145 · 2015: 150 · 2014: 182 · 2013: 166 · 2012: 147
FWCI: 41.99
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2876 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Allergy and Infectious Diseases (R01-AI 60919, R01AI060919)
National Center for Research Resources (1-S10-RR19406, S10RR019406)
Topics: Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords: MAVS, mitochondrial antiviral signaling, NF-κB activation, IRF3 activation, interferon-beta, type I interferon, antiviral innate immunity, RIG-I, CARD domain, transmembrane domain, mitochondrial targeting, IκB phosphorylation, viral RNA sensing, RNAi knockdown
MeSH terms: Amino Acid Sequence, Animals, Cell Line, DNA-Binding Proteins, HeLa Cells, Humans, Immunity, Innate, Interferons, Membrane Proteins, Mitochondria, Molecular Sequence Data, Respirovirus Infections, RNA, Double-Stranded, Transcription Factors, Virus Replication, Signal Transduction, Gene Expression Regulation, Bacterial, NF-kappa B, Sequence Alignment, Interferon-beta, Protein Serine-Threonine Kinases, Gene Silencing, Mitochondrial Proteins, Sendai virus, Interferon Regulatory Factor-3, Interferon Regulatory Factor-7

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Identification and Characterization of MAVS, a Mitochondrial Antiviral Signaling Protein that Activates NF-κB and IRF3

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