Gene Symbol: MDA5
Description: interferon induced with helicase C domain 1
Alias: 9130009C22Rik, Helicard, Hlcd, MDA5, RLR-2, interferon-induced helicase C domain-containing protein 1, RIG-I-like receptor 2, helicase with 2 CARD domains, interferon induced with helicase C domain protein 1, melanoma differentiation-associated protein 5
Species: mouse
Products:     MDA5

Top Publications

  1. Fredericksen B, Keller B, Fornek J, Katze M, Gale M. Establishment and maintenance of the innate antiviral response to West Nile Virus involves both RIG-I and MDA5 signaling through IPS-1. J Virol. 2008;82:609-16 pubmed
    RIG-I and MDA5, two related pathogen recognition receptors (PRRs), are known to be required for sensing various RNA viruses...
  2. Saito T, Owen D, Jiang F, Marcotrigiano J, Gale M. Innate immunity induced by composition-dependent RIG-I recognition of hepatitis C virus RNA. Nature. 2008;454:523-7 pubmed publisher
  3. Kato H, Takeuchi O, Mikamo Satoh E, Hirai R, Kawai T, Matsushita K, et al. Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5. J Exp Med. 2008;205:1601-10 pubmed publisher
    ..acid (RNA) helicases retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) recognize distinct viral and synthetic RNAs, leading to the production of interferons...
  4. Zust R, Cervantes Barragan L, Habjan M, Maier R, Neuman B, Ziebuhr J, et al. Ribose 2'-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5. Nat Immunol. 2011;12:137-43 pubmed publisher
    ..of type I interferon by viruses deficient in 2'-O-methyltransferase was dependent on the cytoplasmic RNA sensor Mda5. This link between Mda5-mediated sensing of viral RNA and 2'-O-methylation of mRNA suggests that RNA modifications ..
  5. Loo Y, Fornek J, Crochet N, Bajwa G, Perwitasari O, Martinez Sobrido L, et al. Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity. J Virol. 2008;82:335-45 pubmed
    ..of the cytoplasmic helicases retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5)...
  6. Gitlin L, Benoit L, Song C, Cella M, Gilfillan S, Holtzman M, et al. Melanoma differentiation-associated gene 5 (MDA5) is involved in the innate immune response to Paramyxoviridae infection in vivo. PLoS Pathog. 2010;6:e1000734 pubmed publisher
    ..Cytoplasmic RNA helicases including RIG-I and MDA5 have been shown to respond to viral RNA by inducing interferon (IFN) production...
  7. Satoh T, Kato H, Kumagai Y, Yoneyama M, Sato S, Matsushita K, et al. LGP2 is a positive regulator of RIG-I- and MDA5-mediated antiviral responses. Proc Natl Acad Sci U S A. 2010;107:1512-7 pubmed publisher
    ..retinoic acid-inducible gene (RIG)-I-like receptors (RLRs), RIG-I, and melanoma differentiation-associated gene 5 (MDA5) in the cytoplasm...
  8. Kovacsovics M, Martinon F, Micheau O, Bodmer J, Hofmann K, Tschopp J. Overexpression of Helicard, a CARD-containing helicase cleaved during apoptosis, accelerates DNA degradation. Curr Biol. 2002;12:838-43 pubmed
    ..Here we report the identification of a widely expressed helicase designated Helicard, which contains two N-terminal CARD domains and a C-terminal helicase domain...
  9. Kang D, Gopalkrishnan R, Wu Q, Jankowsky E, Pyle A, Fisher P. mda-5: An interferon-inducible putative RNA helicase with double-stranded RNA-dependent ATPase activity and melanoma growth-suppressive properties. Proc Natl Acad Sci U S A. 2002;99:637-42 pubmed
    ..MDA-5 is a double-stranded RNA-dependent ATPase that contains both a caspase recruitment domain and RNA helicase motifs, with a confirmed association with growth and differentiation in human melanoma cells. ..

More Information


  1. Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, Matsui K, et al. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature. 2006;441:101-5 pubmed
    ..protein I, also known as Ddx58) and MDA5 (melanoma-differentiation-associated gene 5, also known as Ifih1 or Helicard) have been implicated in viral dsRNA recognition...
  2. Gitlin L, Barchet W, Gilfillan S, Cella M, Beutler B, Flavell R, et al. Essential role of mda-5 in type I IFN responses to polyriboinosinic:polyribocytidylic acid and encephalomyocarditis picornavirus. Proc Natl Acad Sci U S A. 2006;103:8459-64 pubmed
    ..Moreover, mda-5-/- mice exhibited a selectively impaired antiviral response to encephalomyocarditis picornavirus, indicating functional specialization of mda-5 in vivo...
  3. McWhirter S, Barbalat R, Monroe K, Fontana M, Hyodo M, Joncker N, et al. A host type I interferon response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP. J Exp Med. 2009;206:1899-911 pubmed publisher
    ..Our results suggest a novel mechanism by which host cells can induce an inflammatory response to a widely produced bacterial ligand. ..
  4. De Miranda J, Yaddanapudi K, Hornig M, Lipkin W. Astrocytes recognize intracellular polyinosinic-polycytidylic acid via MDA-5. FASEB J. 2009;23:1064-71 pubmed publisher
    ..Our results illustrate the intricacy of extracellular and intracellular ds-RNA recognition in viral infections of the central nervous system and indicate the importance of MDA-5 helicase as an intracellular ds-RNA sensor in astrocytes. ..
  5. Berke I, Modis Y. MDA5 cooperatively forms dimers and ATP-sensitive filaments upon binding double-stranded RNA. EMBO J. 2012;31:1714-26 pubmed publisher
    Melanoma differentiation-associated gene-5 (MDA5) detects viral double-stranded RNA in the cytoplasm...
  6. McCartney S, Vermi W, Gilfillan S, Cella M, Murphy T, Schreiber R, et al. Distinct and complementary functions of MDA5 and TLR3 in poly(I:C)-mediated activation of mouse NK cells. J Exp Med. 2009;206:2967-76 pubmed publisher
    ..acts through two dsRNA sensors, Toll-like receptor 3 (TLR3) and melanoma differentiation-associated protein-5 (MDA5)...
  7. Berke I, Yu X, Modis Y, Egelman E. MDA5 assembles into a polar helical filament on dsRNA. Proc Natl Acad Sci U S A. 2012;109:18437-41 pubmed publisher
    Melanoma differentiation-associated protein 5 (MDA5) detects viral dsRNA in the cytoplasm...
  8. McCartney S, Thackray L, Gitlin L, Gilfillan S, Virgin H, Virgin Iv H, et al. MDA-5 recognition of a murine norovirus. PLoS Pathog. 2008;4:e1000108 pubmed publisher
    ..Because noroviruses are RNA viruses, we investigated whether MDA5 and TLR3, cellular sensors that recognize dsRNA, are important for the host response to MNV-1...
  9. Yount J, Gitlin L, Moran T, LOPEZ C. MDA5 participates in the detection of paramyxovirus infection and is essential for the early activation of dendritic cells in response to Sendai Virus defective interfering particles. J Immunol. 2008;180:4910-8 pubmed
    ..are recognized by more than one viral sensor independently of TLRs and type I IFN signaling; 2) The helicase MDA5 participates in the detection of DI genomes as MDA5-deficient DCs respond inefficiently to Sendai virus stocks ..
  10. Langereis M, Feng Q, van Kuppeveld F. MDA5 localizes to stress granules, but this localization is not required for the induction of type I interferon. J Virol. 2013;87:6314-25 pubmed publisher
    ..of the cytosolic RNA sensors retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5)...
  11. Yoneyama M, Kikuchi M, Matsumoto K, Imaizumi T, Miyagishi M, Taira K, et al. Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. J Immunol. 2005;175:2851-8 pubmed
    ..Melanoma differentiation associated gene 5 (MDA5), which consists of CARD and a helicase domain, functions as a positive regulator, similarly to RIG-I...
  12. Anz D, Thaler R, Stephan N, Waibler Z, Trauscheid M, Scholz C, et al. Activation of melanoma differentiation-associated gene 5 causes rapid involution of the thymus. J Immunol. 2009;182:6044-50 pubmed publisher
    ..We show for the first time that the in vivo activation of the virus-sensing MDA-5 receptor leads to a rapid and reversible involution of the thymus. ..
  13. Li J, Liu Y, Zhang X. Murine coronavirus induces type I interferon in oligodendrocytes through recognition by RIG-I and MDA5. J Virol. 2010;84:6472-82 pubmed publisher
    ..Knockdown of another cytoplasmic receptor, the melanoma-differentiation-associated gene 5 (MDA5), by small interfering RNAs also blocked IFN-beta induction...
  14. Flür K, Allam R, Zecher D, Kulkarni O, Lichtnekert J, Schwarz M, et al. Viral RNA induces type I interferon-dependent cytokine release and cell death in mesangial cells via melanoma-differentiation-associated gene-5: Implications for viral infection-associated glomerulonephritis. Am J Pathol. 2009;175:2014-22 pubmed publisher
    ..their mitochondrial adaptor IFN-beta promoter stimulator-1 as well, and small interfering RNA studies revealed that MDA5 but not RIG-I was required for cytosolic poly I:C RNA signaling...
  15. Poeck H, Bscheider M, Gross O, Finger K, Roth S, Rebsamen M, et al. Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1 beta production. Nat Immunol. 2010;11:63-9 pubmed publisher
    ..Our results identify the CARD9-Bcl-10 module as an essential component of the RIG-I-dependent proinflammatory response and establish RIG-I as a sensor able to activate the inflammasome in response to certain RNA viruses. ..
  16. Philip J, Xu Z, Bowles N, Vallejo J. Cardiac-specific overexpression of melanoma differentiation-associated gene-5 protects mice from lethal viral myocarditis. Circ Heart Fail. 2013;6:326-34 pubmed publisher
    ..The RNA helicase melanoma differentiation-associated gene-5 (MDA5) is critical for host antiviral responses against members of the Picornaviridae family, such as ..
  17. Narayan K, Waggoner L, Pham S, Hendricks G, Waggoner S, Conlon J, et al. TRIM13 is a negative regulator of MDA5-mediated type I interferon production. J Virol. 2014;88:10748-57 pubmed publisher
    Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are essential intracellular detectors of viral RNA...
  18. Asdonk T, Steinmetz M, Krogmann A, Ströcker C, Lahrmann C, Motz I, et al. MDA-5 activation by cytoplasmic double-stranded RNA impairs endothelial function and aggravates atherosclerosis. J Cell Mol Med. 2016;20:1696-705 pubmed publisher
    ..Thus, the spectrum of relevant innate immune receptors in vascular diseases and atherogenesis might not be restricted to TLRs but also encompasses the group of RLRs including MDA-5. ..
  19. Miyamoto M, Komuro A. PACT is required for MDA5-mediated immunoresponses triggered by Cardiovirus infection via interaction with LGP2. Biochem Biophys Res Commun. 2017;494:227-233 pubmed publisher
    Laboratory of genetics and physiology 2 (LGP2) and melanoma differentiation-associated gene 5 (MDA5) cooperatively detect viral RNA in the cytoplasm of Cardiovirus-infected cells and activate innate immune responses...
  20. Hayashi Y, Onomoto K, Narita R, Yoneyama M, Kato H, Nakagawa T, et al. Virus-induced expression of retinoic acid inducible gene-I and melanoma differentiation-associated gene 5 in the cochlear sensory epithelium. Microbes Infect. 2013;15:592-8 pubmed publisher
    ..the potential involvement of retinoic acid inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5), which are critical for initiating antiviral innate immune responses...
  21. Lazear H, Pinto A, RAMOS H, Vick S, Shrestha B, Suthar M, et al. Pattern recognition receptor MDA5 modulates CD8+ T cell-dependent clearance of West Nile virus from the central nervous system. J Virol. 2013;87:11401-15 pubmed publisher
    ..Although two members of the RLR family, RIG-I and MDA5, have been implicated in host control of virus infection, the relative role of each RLR in restricting pathogenesis ..
  22. Anz D, Koelzer V, Moder S, Thaler R, Schwerd T, Lahl K, et al. Immunostimulatory RNA blocks suppression by regulatory T cells. J Immunol. 2010;184:939-46 pubmed publisher
    ..Thus, we show in this study for the first time that activation of a RIG-I-like helicase on Treg cells blocks their suppressive function. ..
  23. Poeck H, Besch R, Maihoefer C, Renn M, Tormo D, Morskaya S, et al. 5'-Triphosphate-siRNA: turning gene silencing and Rig-I activation against melanoma. Nat Med. 2008;14:1256-63 pubmed publisher
  24. Duewell P, Steger A, Lohr H, Bourhis H, Hoelz H, Kirchleitner S, et al. RIG-I-like helicases induce immunogenic cell death of pancreatic cancer cells and sensitize tumors toward killing by CD8(+) T cells. Cell Death Differ. 2014;21:1825-37 pubmed publisher
    ..Vaccination of mice with RLH-activated tumor cells induced protective antitumor immunity in vivo. In addition, MDA5-based immunotherapy led to effective tumor control of established pancreatic tumors...
  25. Crampton S, Deane J, Feigenbaum L, Bolland S. Ifih1 gene dose effect reveals MDA5-mediated chronic type I IFN gene signature, viral resistance, and accelerated autoimmunity. J Immunol. 2012;188:1451-9 pubmed publisher
    ..a new transgenic mouse line containing multiple copies of Ifih1, a gene encoding the cytoplasmic dsRNA sensor MDA5 with proven linkage to diabetes and lupus...
  26. Hühn M, McCartney S, Lind K, Svedin E, Colonna M, Flodstrom Tullberg M. Melanoma differentiation-associated protein-5 (MDA-5) limits early viral replication but is not essential for the induction of type 1 interferons after Coxsackievirus infection. Virology. 2010;401:42-8 pubmed publisher
    ..Taken together, our findings indicate that MDA-5 plays an important role in the host immune response to CVB3 by preventing early virus replication and limiting tissue pathology. ..
  27. Zalinger Z, Elliott R, Rose K, Weiss S. MDA5 Is Critical to Host Defense during Infection with Murine Coronavirus. J Virol. 2015;89:12330-40 pubmed publisher
    ..mouse hepatitis virus (MHV) activates the pattern recognition receptors melanoma differentiation-associated gene 5 (MDA5) and Toll-like receptor 7 (TLR7) to induce transcription of type I interferon...
  28. Pham A, Santa Maria F, Lahiri T, Friedman E, Marié I, Levy D. PKR Transduces MDA5-Dependent Signals for Type I IFN Induction. PLoS Pathog. 2016;12:e1005489 pubmed publisher
    ..Two cytosolic RIG-like RNA helicases, RIG-I and MDA5, are key to type I interferon (IFN) induction in response to viral infection...
  29. Broquet A, Hirata Y, McAllister C, Kagnoff M. RIG-I/MDA5/MAVS are required to signal a protective IFN response in rotavirus-infected intestinal epithelium. J Immunol. 2011;186:1618-26 pubmed publisher
    ..which interact with either retinoic acid-inducible gene I (RIG-I) or melanoma differentiation-associated gene 5 (MDA5) inside cells, rotavirus was sensed by both RIG-I and MDA5, alone and in combination...
  30. Goubau D, Schlee M, Deddouche S, Pruijssers A, Zillinger T, Goldeck M, et al. Antiviral immunity via RIG-I-mediated recognition of RNA bearing 5'-diphosphates. Nature. 2014;514:372-375 pubmed publisher
    ..In the cytosol, the RIG-I-like receptors (RLRs), RIG-I (retinoic acid-inducible gene I; encoded by DDX58) and MDA5 (melanoma differentiation-associated gene 5; encoded by IFIH1) sense atypical RNAs associated with virus infection...
  31. Jin Y, Kim S, So E, Meng L, Colonna M, Kim B. Melanoma differentiation-associated gene 5 is critical for protection against Theiler's virus-induced demyelinating disease. J Virol. 2012;86:1531-43 pubmed publisher
    ..virus (TMEV) induces various cytokines via Toll-like receptor- and melanoma differentiation-associated gene 5 (MDA5)-dependent pathways...
  32. Tarallo V, Hirano Y, Gelfand B, Dridi S, Kerur N, Kim Y, et al. DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88. Cell. 2012;149:847-59 pubmed publisher
    ..Our findings also reveal a function of the inflammasome outside the immune system and an immunomodulatory action of mobile elements. ..
  33. Wu J, Tian L, Yu X, Pattaradilokrat S, Li J, Wang M, et al. Strain-specific innate immune signaling pathways determine malaria parasitemia dynamics and host mortality. Proc Natl Acad Sci U S A. 2014;111:E511-20 pubmed publisher
  34. Menachery V, Yount B, Josset L, Gralinski L, Scobey T, Agnihothram S, et al. Attenuation and restoration of severe acute respiratory syndrome coronavirus mutant lacking 2'-o-methyltransferase activity. J Virol. 2014;88:4251-64 pubmed publisher
    ..However, the absence of either MDA5 or IFIT1, IFN-responsive genes that recognize unmethylated 2'-O RNA, resulted in restored replication and virulence ..
  35. Errett J, Suthar M, McMillan A, Diamond M, Gale M. The essential, nonredundant roles of RIG-I and MDA5 in detecting and controlling West Nile virus infection. J Virol. 2013;87:11416-25 pubmed publisher
    ..adaptive immunity against West Nile virus (WNV), an emerging vector-borne virus, depend on recognition by RIG-I and MDA5, two cytosolic pattern recognition receptors (PRRs) of the RIG-I-like receptor (RLR) protein family that recognize ..
  36. Hu M, Liao C, Yang Q, Xie X, Shu H. Innate immunity to RNA virus is regulated by temporal and reversible sumoylation of RIG-I and MDA5. J Exp Med. 2017;214:973-989 pubmed publisher
    Sensing of viral RNA by the cytosolic receptors RIG-I and melanoma differentiation-associated gene 5 (MDA5) leads to innate antiviral response...
  37. Ernst P, Fisher J, Avery W, Wade S, Foy D, Korsmeyer S. Definitive hematopoiesis requires the mixed-lineage leukemia gene. Dev Cell. 2004;6:437-43 pubmed
    ..These results demonstrate an intrinsic requirement for MLL in definitive hematopoiesis, where it is essential for the generation of HSCs in the embryo. ..
  38. Ruane D, Brane L, Reis B, Cheong C, Poles J, Do Y, et al. Lung dendritic cells induce migration of protective T cells to the gastrointestinal tract. J Exp Med. 2013;210:1871-88 pubmed publisher
    ..The present report demonstrates novel functional evidence of mucosal cross talk mediated by DCs, which has the potential to inform the design of novel vaccines against mucosal pathogens. ..
  39. Wang Y, Cella M, Gilfillan S, Colonna M. Cutting edge: polyinosinic:polycytidylic acid boosts the generation of memory CD8 T cells through melanoma differentiation-associated protein 5 expressed in stromal cells. J Immunol. 2010;184:2751-5 pubmed publisher
    ..Poly I:C is sensed by both TLR3 in the endosomes and melanoma differentiation-associated protein 5 (MDA5) in the cytoplasm...
  40. Gibbert K, Dietze K, Zelinskyy G, Lang K, Barchet W, Kirschning C, et al. Polyinosinic-polycytidylic acid treatment of Friend retrovirus-infected mice improves functional properties of virus-specific T cells and prevents virus-induced disease. J Immunol. 2010;185:6179-89 pubmed publisher
    ..Along these lines, the TLR3/MDA5 ligand polyinosinic-polycytidylic acid [poly(I:C)] has already been used to treat viral infections...
  41. Gorman J, Hundhausen C, Errett J, STONE A, Allenspach E, Ge Y, et al. The A946T variant of the RNA sensor IFIH1 mediates an interferon program that limits viral infection but increases the risk for autoimmunity. Nat Immunol. 2017;18:744-752 pubmed publisher
  42. Faul E, Wanjalla C, Suthar M, Gale M, Wirblich C, Schnell M. Rabies virus infection induces type I interferon production in an IPS-1 dependent manner while dendritic cell activation relies on IFNAR signaling. PLoS Pathog. 2010;6:e1001016 pubmed publisher
    ..We see that IPS-1-/- mice are more susceptible to infection than IPS-1+/+ mice and have a significantly increased incident of limb paralysis. ..
  43. Fukuda M, Ushio H, Kawasaki J, Niyonsaba F, Takeuchi M, Baba T, et al. Expression and functional characterization of retinoic acid-inducible gene-I-like receptors of mast cells in response to viral infection. J Innate Immun. 2013;5:163-73 pubmed publisher
    ..bone marrow-derived mast cells (BMMCs) revealed that BMMCs express melanoma differentiation-associated gene 5 (MDA5), protein kinase RNA-activated, retinoic acid-inducible gene-I (RIG-I) and Toll-like receptor 3...
  44. Abdullah Z, Schlee M, Roth S, Mraheil M, Barchet W, Böttcher J, et al. RIG-I detects infection with live Listeria by sensing secreted bacterial nucleic acids. EMBO J. 2012;31:4153-64 pubmed publisher
    ..released nucleic acids and that such secreted bacterial RNA/DNA was recognized by the cytosolic sensors RIG-I, MDA5 and STING thereby triggering interferon ? production...
  45. Dewitte Orr S, Collins S, Bauer C, Bowdish D, Mossman K. An accessory to the 'Trinity': SR-As are essential pathogen sensors of extracellular dsRNA, mediating entry and leading to subsequent type I IFN responses. PLoS Pathog. 2010;6:e1000829 pubmed publisher
    ..Furthermore, the implications of a cell surface receptor capable of recognizing extracellular RNA may exceed beyond viral immunity to mediating other important innate immune functions. ..
  46. Burel S, Machemer T, Ragone F, Kato H, Cauntay P, Greenlee S, et al. Unique O-methoxyethyl ribose-DNA chimeric oligonucleotide induces an atypical melanoma differentiation-associated gene 5-dependent induction of type I interferon response. J Pharmacol Exp Ther. 2012;342:150-62 pubmed publisher
    ..Pretreatment of mice with melanoma differentiation-associated gene 5 (MDA5) and IFN-? promoter stimulator-1 ASOs, but not RIG-I or laboratory of genetics and physiology 2 (LGP2) ASOs, ..
  47. Chiang H, Zhao Y, Song J, Liu S, Wang N, Terhorst C, et al. GEF-H1 controls microtubule-dependent sensing of nucleic acids for antiviral host defenses. Nat Immunol. 2014;15:63-71 pubmed publisher
    ..Activation of GEF-H1 controls RIG-I-dependent and Mda5-dependent phosphorylation of IRF3 and induction of IFN-? expression in macrophages...
  48. Roth Cross J, Bender S, Weiss S. Murine coronavirus mouse hepatitis virus is recognized by MDA5 and induces type I interferon in brain macrophages/microglia. J Virol. 2008;82:9829-38 pubmed publisher
    ..Interestingly, MDA5, a PRR thought to recognize primarily picornaviruses, was required for recognition of MHV...
  49. Wang J, Cerny A, Asher D, Kurt Jones E, Bronson R, Finberg R. MDA5 and MAVS mediate type I interferon responses to coxsackie B virus. J Virol. 2010;84:254-60 pubmed publisher
    ..In the present study, we found that MDA5 and its adaptor molecule MAVS are critical for type I interferon responses to CVB, since the absence of either MAVS ..
  50. Lincez P, Shanina I, Horwitz M. Reduced expression of the MDA5 Gene IFIH1 prevents autoimmune diabetes. Diabetes. 2015;64:2184-93 pubmed publisher expression of the intracellular RNA virus sensor known as melanoma differentiation-associated protein 5 (MDA5). Here, we translate the reduction in IFIH1 gene expression that results in protection from T1D...
  51. Chattopadhyay S, Marques J, Yamashita M, Peters K, Smith K, Desai A, et al. Viral apoptosis is induced by IRF-3-mediated activation of Bax. EMBO J. 2010;29:1762-73 pubmed publisher
    ..Thus, IRF-3 is a dual-action cytoplasmic protein that, upon activation, translocates to the nucleus or to the mitochondrion and triggers two complementary antiviral responses of the infected cell. ..
  52. Kitai Y, Takeuchi O, Kawasaki T, Ori D, Sueyoshi T, Murase M, et al. Negative regulation of melanoma differentiation-associated gene 5 (MDA5)-dependent antiviral innate immune responses by Arf-like protein 5B. J Biol Chem. 2015;290:1269-80 pubmed publisher
    RIG-I-like receptors (RLRs), including retinoic acid-inducible gene-I (RIG-I) and MDA5, constitute a family of cytoplasmic RNA helicases that senses viral RNA and mounts antiviral innate immunity by producing type I interferons and ..
  53. Ermler M, Yerukhim E, Schriewer J, Schattgen S, Traylor Z, Wespiser A, et al. RNA helicase signaling is critical for type i interferon production and protection against Rift Valley fever virus during mucosal challenge. J Virol. 2013;87:4846-60 pubmed publisher
    ..In addition, we demonstrate that Toll-like-receptor-mediated signaling is not involved in IFN production, further emphasizing the importance of the RNA cellular helicases in type I IFN responses to RVFV. ..
  54. Lu H, Liao F. Melanoma differentiation-associated gene 5 senses hepatitis B virus and activates innate immune signaling to suppress virus replication. J Immunol. 2013;191:3264-76 pubmed publisher
    Retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) belong to the RIG-I-like receptors family of pattern recognition receptors...
  55. Wies E, Wang M, Maharaj N, Chen K, Zhou S, Finberg R, et al. Dephosphorylation of the RNA sensors RIG-I and MDA5 by the phosphatase PP1 is essential for innate immune signaling. Immunity. 2013;38:437-49 pubmed publisher
    RIG-I and MDA5 have emerged as key cytosolic sensors for the detection of RNA viruses and lead to antiviral interferon (IFN) production...
  56. Dou Y, Yim H, Kirkwood C, Williams B, Sadler A. The innate immune receptor MDA5 limits rotavirus infection but promotes cell death and pancreatic inflammation. EMBO J. 2017;36:2742-2757 pubmed publisher
    Melanoma differentiation-associated protein 5 (MDA5) mediates the innate immune response to viral infection. Polymorphisms in IFIH1, the gene coding for MDA5, correlate with the risk of developing type 1 diabetes (T1D)...
  57. Motz C, Schuhmann K, Kirchhofer A, Moldt M, Witte G, Conzelmann K, et al. Paramyxovirus V proteins disrupt the fold of the RNA sensor MDA5 to inhibit antiviral signaling. Science. 2013;339:690-3 pubmed publisher
    The retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) melanoma differentiation-associated protein 5 (MDA5) senses cytoplasmic viral RNA and activates antiviral innate immunity...
  58. Miyashita M, Oshiumi H, Matsumoto M, Seya T. DDX60, a DEXD/H box helicase, is a novel antiviral factor promoting RIG-I-like receptor-mediated signaling. Mol Cell Biol. 2011;31:3802-19 pubmed publisher
    The cytoplasmic viral RNA sensors RIG-I and MDA5 are important for the production of type I interferon and other inflammatory cytokines...
  59. Lang X, Tang T, Jin T, Ding C, Zhou R, Jiang W. TRIM65-catalized ubiquitination is essential for MDA5-mediated antiviral innate immunity. J Exp Med. 2017;214:459-473 pubmed publisher
    b>MDA5 plays a critical role in antiviral innate immunity by functioning as a cytoplasmic double-stranded RNA sensor that can activate type I interferon signaling pathways, but the mechanism for the activation of MDA5 is poorly understood...
  60. Kim H, Kim C, Kim M, Ryu J, Seong S, Kim S, et al. The Induction of Pattern-Recognition Receptor Expression against Influenza A Virus through Duox2-Derived Reactive Oxygen Species in Nasal Mucosa. Am J Respir Cell Mol Biol. 2015;53:525-35 pubmed publisher
    ..for the induction of retinoic acid-inducible gene (RIG)-I and melanoma differentiation-associated protein 5 (MDA5) transcription...
  61. Sharma S, Deoliveira R, Kalantari P, Parroche P, Goutagny N, Jiang Z, et al. Innate immune recognition of an AT-rich stem-loop DNA motif in the Plasmodium falciparum genome. Immunity. 2011;35:194-207 pubmed publisher
    ..Collectively, these observations implicate AT-rich DNA sensing via STING, TBK1 and IRF3-IRF7 in P. falciparum malaria. ..
  62. Pestal K, Funk C, Snyder J, Price N, Treuting P, Stetson D. Isoforms of RNA-Editing Enzyme ADAR1 Independently Control Nucleic Acid Sensor MDA5-Driven Autoimmunity and Multi-organ Development. Immunity. 2015;43:933-44 pubmed publisher
    ..Here, we demonstrate that ADAR1 is a specific and essential negative regulator of the MDA5-MAVS RNA sensing pathway...
  63. Swanson C, Wilson T, Strauch P, Colonna M, Pelanda R, Torres R. Type I IFN enhances follicular B cell contribution to the T cell-independent antibody response. J Exp Med. 2010;207:1485-500 pubmed publisher
    ..Thus, innate signals have the capacity to enhance TI-2 antibody responses by promoting participation of FO B cells, which then elaborate effective IgG anti-pathogen antibodies. ..
  64. Tzeng H, Tsai H, Chyuan I, Liao H, Chen C, Chen P, et al. Tumor necrosis factor-alpha induced by hepatitis B virus core mediating the immune response for hepatitis B viral clearance in mice model. PLoS ONE. 2014;9:e103008 pubmed publisher
    ..Our results demonstrate that HBV viral clearance is not changed in IFN-?/? receptor (IFNAR), RIG-I, MDA5, MYD88, NLRP3, ASC, and IL-1R knock-out mice, indicating that these innate immunity effectors are not required for ..
  65. Monroe K, McWhirter S, Vance R. Identification of host cytosolic sensors and bacterial factors regulating the type I interferon response to Legionella pneumophila. PLoS Pathog. 2009;5:e1000665 pubmed publisher
    ..We provide genetic evidence that two RNA-sensing proteins, RIG-I and MDA5, participate in the IFN response to L. pneumophila...
  66. Pantel A, Teixeira A, Haddad E, Wood E, Steinman R, Longhi M. Direct type I IFN but not MDA5/TLR3 activation of dendritic cells is required for maturation and metabolic shift to glycolysis after poly IC stimulation. PLoS Biol. 2014;12:e1001759 pubmed publisher
    ..In contrast to direct TLR3/mda5 signaling, IFNs are required for upregulation of all pathways associated with DC immunogenicity...
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    ..This dialog may be affected by the individual's genetic background. We presently evaluated whether modulation of MDA5 and PTPN2, two candidate genes for T1D, affects beta-cell responses to double-stranded RNA (dsRNA), a by-product of ..
  68. Jelinek I, Leonard J, Price G, Brown K, Meyer Manlapat A, Goldsmith P, et al. TLR3-specific double-stranded RNA oligonucleotide adjuvants induce dendritic cell cross-presentation, CTL responses, and antiviral protection. J Immunol. 2011;186:2422-9 pubmed publisher
    ..These results provide the basis for the development of TLR3-specific adjuvants capable of inducing immune responses tailored for viral pathogens. ..
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    ..Therefore, ZAP is an RNA-sensing anti-viral effector molecule that mediates the type-I-IFN-dependent host defense against SINV. ..
  70. Nikonov A, Mölder T, Sikut R, Kiiver K, Männik A, Toots U, et al. RIG-I and MDA-5 detection of viral RNA-dependent RNA polymerase activity restricts positive-strand RNA virus replication. PLoS Pathog. 2013;9:e1003610 pubmed publisher
    ..These results suggest that host cells can restrict RNA virus replication by detecting the products of unspecific viral replicase RdRp activity. ..
  71. Tamassia N, Le Moigne V, Rossato M, Donini M, McCartney S, Calzetti F, et al. Activation of an immunoregulatory and antiviral gene expression program in poly(I:C)-transfected human neutrophils. J Immunol. 2008;181:6563-73 pubmed human neutrophils) or with cytoplasmic RNA helicases such as melanoma differentiation-associated gene 5 (MDA5) and retinoic acid-inducible gene I (RIG-I)...
  72. Oda H, Nakagawa K, Abe J, Awaya T, Funabiki M, Hijikata A, et al. Aicardi-Goutières syndrome is caused by IFIH1 mutations. Am J Hum Genet. 2014;95:121-5 pubmed publisher
    ..IFIH1 encodes MDA5, and mutant MDA5 lacked ligand-specific responsiveness, similarly to the dominant Ifih1 mutation responsible for ..
  73. Funabiki M, Kato H, Miyachi Y, Toki H, Motegi H, Inoue M, et al. Autoimmune disorders associated with gain of function of the intracellular sensor MDA5. Immunity. 2014;40:199-212 pubmed publisher
    b>MDA5 is an essential intracellular sensor for several viruses, including picornaviruses, and elicits antiviral interferon (IFN) responses by recognizing viral dsRNAs. MDA5 has been implicated in autoimmunity...
  74. Abe Y, Fujii K, Nagata N, Takeuchi O, Akira S, Oshiumi H, et al. The toll-like receptor 3-mediated antiviral response is important for protection against poliovirus infection in poliovirus receptor transgenic mice. J Virol. 2012;86:185-94 pubmed publisher
    ..We observed that alpha/beta interferon (IFN-?/?) production in response to PV infection occurred in an MDA5-dependent but RIG-I-independent manner in primary cultured kidney cells in vitro...