Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

MAVS-Mitochondrial Antiviral Signaling Protein

  • Michael P. Mohning
  • Shaikh Muhammad AtifEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101513

Historical Background

Adaptor proteins are crucial members of signaling cascades that bind to multiple pattern recognition receptors to streamline the inflammatory response. One such adaptor molecule is MAVS (also known as IPS1, VISA, or CARDIF), which is present downstream of RIG-I and MDA-5, cytosolic sensors of viral genomic material (Seth et al. 2005). In the year 2005, several groups independently identified an adaptor protein that controls activation of IKK and TBK1/IKKε downstream of RIG-I. This adaptor molecule was named MAVS (Seth et al. 2005), IPS-1 (Kawai et al. 2005), VISA (Xu et al. 2005), or CARDIF (Meylan et al. 2005). However, MAVS is now the standard nomenclature accepted in the scientific community. Upon activation, MAVS initiates downstream signaling cascades leading to the production of inflammatory cytokines, antimicrobial peptides, and activation of several transcription factors (Li et al. 2011). Its importance is now recognized not only in viral infection but...

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  1. Cao Z, Zhou Y, Zhu S, Feng J, Chen X, Liu S, Peng N, Yang X, Xu G, Zhu Y. Pyruvate carboxylase activates the RIG-I-like receptor-mediated antiviral immune response by targeting the MAVS signalosome. Sci Rep. 2016;6:22002.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Dann A, Poeck H, Croxford AL, Gaupp S, Kierdorf K, Knust M, Pfeifer D, Maihoefer C, Endres S, Kalinke U, Meuth SG, Wiendl H, Knobeloch KP, Akira S, Waisman A, Hartmann G, Prinz M. Cytosolic RIG-I-like helicases act as negative regulators of sterile inflammation in the CNS. Nat Neurosci. 2011;15(1):98–106.CrossRefPubMedGoogle Scholar
  3. Fitzgerald KA, et al. IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat Immunol. 2003;4:491–6.CrossRefPubMedGoogle Scholar
  4. Goritzka M, Makris S, Kausar F, Durant LR, Pereira C, Kumagai Y, Culley FJ, Mack M, Akira S, Johansson C. Alveolar macrophage-derived type I interferons orchestrate innate immunity to RSV through recruitment of antiviral monocytes. J Exp Med. 2015;212(5):699–714.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Guan K, Zheng Z, Song T, He X, Xu C, Zhang Y, Ma S, Wang Y, Xu Q, Cao Y, Li J, Yang X, Ge X, Wei C, Zhong H. MAVS regulates apoptotic cell death by decreasing K48-linked ubiquitination of voltage-dependent anion channel 1. Mol Cell Biol. 2013;33(16):3137–49.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Guo B, Cheng G. Modulation of the interferon antiviral response by the TBK1/IKKi adaptor protein TANK. J Biol Chem. 2007;282:11817–26.CrossRefPubMedGoogle Scholar
  7. Haynes LD, Verma S, McDonald B, Wu R, Tacke R, Nowyhed HN, Ekstein J, Feuvrier A, Benedict CA, Hedrick CC. Cardif (MAVS) regulates the maturation of NK cells. J Immunol. 2015;195(5):2157–67.PubMedPubMedCentralCrossRefGoogle Scholar
  8. He Z, Zhu X, Wen W, Yuan J, Hu Y, Chen J, An S, Dong X, Lin C, Yu J, Wu J, Yang Y, Cai J, Li J, Li M. Dengue virus subverts host innate immunity by targeting adaptor protein MAVS. J Virol. 2016;90(16):7219–30.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Hou F, Sun L, Zheng H, Skaug B, Jiang QX, Chen ZJ. MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response. Cell. 2011;146(3):448–61.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Jia Y, Song T, Wei C, Ni C, Zheng Z, Xu Q, Ma H, Li L, Zhang Y, He X, Xu Y, Shi W, Zhong H. Negative regulation of MAVS-mediated innate immune response by PSMA7. J Immunol. 2009;183(7):4241–8.CrossRefPubMedGoogle Scholar
  11. Kawai T, Takahashi K, Sato S, Coban C, Kumar H, Kato H, Ishii KJ, Takeuchi O, Akira S. IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nat Immunol. 2005;6(10):981–8.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Li XD, Sun L, Seth RB, Pineda G, Chen ZJ. Hepatitis C virus protease NS3/4A cleaves mitochondrial antiviral signaling protein off the mitochondria to evade innate immunity. Proc Natl Acad Sci USA. 2005;102(49):17717–22.CrossRefGoogle Scholar
  13. Li XD, Chiu YH, Ismail AS, Behrendt CL, Wight-Carter M, Hooper LV, Chen ZJ. Mitochondrial antiviral signaling protein (MAVS) monitors commensal bacteria and induces an immune response that prevents experimental colitis. Proc Natl Acad Sci USA. 2011;108(42):17390–5.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Liu XY, Wei B, Shi HX, Shan YF, Wang C. Tom70 mediates activation of interferon regulatory factor 3 on mitochondria. Cell Res. 2010;20(9):994–1011.CrossRefPubMedGoogle Scholar
  15. McDonald B, Pittman K, Menezes GB, Hirota SA, Slaba I, Waterhouse CC, Beck PL, Muruve DA, Kubes P. Intravascular danger signals guide neutrophils to sites of sterile inflammation. Science. 2010;330(6002):362–6.  https://doi.org/10.1126/science.1195491. Erratum in: Science. 2011;331(6024):1517.CrossRefGoogle Scholar
  16. Meylan E, Curran J, Hofmann K, Moradpour D, Binder M, Bartenschlager R, Tschopp J. Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature. 2005;437(7062):1167–72.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Michallet MC, et al. TRADD protein is an essential component of the RIG-like helicase antiviral pathway. Immunity. 2008;28:651–61.CrossRefPubMedGoogle Scholar
  18. Pan Y, Li R, Meng JL, Mao HT, Zhang Y, Zhang J. Smurf2 negatively modulates RIG-I-dependent antiviral response by targeting VISA/MAVS for ubiquitination and degradation. J Immunol. 2014;192(10):4758–64.CrossRefPubMedGoogle Scholar
  19. Potter JA, Randall RE, Taylor GL. Crystal structure of human IPS-1/MAVS/VISA/Cardif caspase activation recruitment domain. BMC Struct Biol. 2008;8:11.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Satoh T, Kato H, Kumagai Y, Yoneyama M, Sato S, Matsushita K, Tsujimura T, Fujita T, Akira S, Takeuchi O. LGP2 is a positive regulator of RIG-I- and MDA5-mediated antiviral responses. Proc Natl Acad Sci USA. 2010;107(4):1512–7.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Seth RB, Sun L, Ea C-K, Chen ZJ. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-κB and IRF3. Cell. 2005;122(5):669–82.PubMedPubMedCentralCrossRefGoogle Scholar
  22. Su YJ, Cheng TT, Chen CJ, Chang WN, Tsai NW, Kung CT, Wang HC, Lin WC, Huang CC, Chang YT, Su CM, Chiang YF, Cheng BC, Lin YJ, Lu CH. Investigation of the caspase-dependent mitochondrial apoptotic pathway in mononuclear cells of patients with systemic Lupus erythematosus. J Transl Med. 2014;12:303.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Takeuchi O, Akira S. MDA5/RIG-I and virus recognition. Curr Opin Immunol. 2008;20(1):17–22.CrossRefPubMedGoogle Scholar
  24. Tang ED, Wang C-Y. MAVS self-association mediates antiviral innate immune signaling. J Virol. 2009;83:3420–8.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Tang ED, Wang C-Y. TRAF5 is a downstream target of MAVS in antiviral innate immune signaling. PLoS One. 2010;5(2):e9172.PubMedPubMedCentralCrossRefGoogle Scholar
  26. West AP, Shadel GS, Ghosh S. Mitochondria in innate immune responses. Nat Rev Immunol. 2011;11(6):389–402.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Xu LG, Wang YY, Han KJ, Li LY, Zhai Z, Shu HB. VISA is an adapter protein required for virus-triggered IFN-beta signaling. Mol Cell. 2005;19(6):727–40.PubMedPubMedCentralCrossRefGoogle Scholar
  28. Xu L, Xiao N, Liu F, Ren H, Gu J. Inhibition of RIG-I and MDA5-dependent antiviral response by gC1qR at mitochondria. Proc Natl Acad Sci USA. 2009;106:1530–5.PubMedPubMedCentralCrossRefGoogle Scholar
  29. You F, Sun H, Zhou X, et al. PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiquitin ligase AIP4. Nat Immunol. 2009;10:1300–8.CrossRefPubMedGoogle Scholar
  30. Zhao J, Vijay R, Zhao J, Gale Jr M, Diamond MS, Perlman S. MAVS expressed by hematopoietic cells is critical for control of West Nile virus infection and pathogenesis. J Virol. 2016;90(16):7098–108.PubMedPubMedCentralCrossRefGoogle Scholar
  31. Zhong B, Yang Y, Li S, Wang YY, Li Y, Diao F, Lei C, He X, Zhang L, Tien P, Shu HB. The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation. Immunity. 2008;29:538–50.CrossRefGoogle Scholar
  32. Zhou X, You F, Chen H, Jiang Z. Poly(C)-binding protein 1 (PCBP1) mediates housekeeping degradation of mitochondrial antiviral signaling (MAVS). Cell Res. 2012;22(4):717–27.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of MedicineNational Jewish HealthDenverUSA
  2. 2.Department of PediatricsNational Jewish HealthDenverUSA