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Virologica Sinica

, Volume 30, Issue 3, pp 163–173 | Cite as

Emerging complexity and new roles for the RIG-I-like receptors in innate antiviral immunity

  • John S. Errett
  • Michael Gale
Review

Abstract

Innate immunity is critical for the control of virus infection and operates to restrict viral susceptibility and direct antiviral immunity for protection from acute or chronic viral-associated diseases including cancer. RIG-I like receptors (RLRs) are cytosolic RNA helicases that function as pathogen recognition receptors to detect RNA pathogen associated molecular patterns (PAMPs) of virus infection. The RLRs include RIG-I, MDA5, and LGP2. They function to recognize and bind to PAMP motifs within viral RNA in a process that directs the RLR to trigger downstream signaling cascades that induce innate immunity that controls viral replication and spread. Products of RLR signaling also serve to modulate the adaptive immune response to infection. Recent studies have additionally connected RLRs to signaling cascades that impart inflammatory and apoptotic responses to virus infection. Viral evasion of RLR signaling supports viral outgrowth and pathogenesis, including the onset of viral-associated cancer.

Keywords

RIG-I MDA5 pattern recognition receptor pathogen associated molecular pattern innate immunity virus infection 

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References

  1. Ablasser A, Bauernfeind F, Hartmann G, Latz E, Fitzgerald KA, Hornung V. 2009. RIG-I-dependent sensing of poly(dA:dT) through the induction of an RNA polymerase III-transcribed RNA intermediate. Nat Immunol, 10: 1065–1072.PubMedGoogle Scholar
  2. Ablasser A, Goldeck M, Cavlar T, Deimling T, Witte G, Rohl I, Hopfner KP, Ludwig J, Hornung V. 2013. cGAS produces a 2'-5'-linked cyclic dinucleotide second messenger that activates STING. Nature, 498: 380–384.PubMedCentralPubMedGoogle Scholar
  3. Andersson U, Erlandsson-Harris H, Yang H, Tracey KJ. 2002. HMGB1 as a DNA-binding cytokine. J Leukoc Biol, 72: 1084–1091.PubMedGoogle Scholar
  4. Andrejeva J, Childs KS, Young DF, Carlos TS, Stock N, Goodbourn S, Randall RE. 2004. The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-beta promoter. Proc Natl Acad Sci U S A, 101: 17264–17269.PubMedCentralPubMedGoogle Scholar
  5. Ariumi Y, Kuroki M, Abe K, Dansako H, Ikeda M, Wakita T, Kato N. 2007. DDX3 DEAD-box RNA helicase is required for hepatitis C virus RNA replication. J Virol, 81: 13922–13926.PubMedCentralPubMedGoogle Scholar
  6. Barbalat R, Lau L, Locksley RM, Barton GM. 2009. Toll-like receptor 2 on inflammatory monocytes induces type I interferon in response to viral but not bacterial ligands. Nat Immunol, 10: 1200–1207.PubMedCentralPubMedGoogle Scholar
  7. Barral PM, Sarkar D, Fisher PB, Racaniello VR. 2009. RIG-I is cleaved during picornavirus infection. Virology, 391: 171–176.PubMedCentralPubMedGoogle Scholar
  8. Berke IC, Modis Y. 2012. MDA5 cooperatively forms dimers and ATP-sensitive filaments upon binding double-stranded RNA. EMBO J, 31: 1714–1726.PubMedCentralPubMedGoogle Scholar
  9. Besch R, Poeck H, Hohenauer T, Senft D, Hacker G, Berking C, Hornung V, Endres S, Ruzicka T, Rothenfusser S, Hartmann G. 2009. Proapoptotic signaling induced by RIG-I and MDA-5 results in type I interferon-independent apoptosis in human melanoma cells. J Clin Invest, 119: 2399–2411.PubMedCentralPubMedGoogle Scholar
  10. Brunette RL, Young JM, Whitley DG, Brodsky IE, Malik HS, Stetson DB. 2012. Extensive evolutionary and functional diversity among mammalian AIM2-like receptors. J Exp Med, 209: 1969–1983.PubMedCentralPubMedGoogle Scholar
  11. Cheng G, Zhong J, Chung J, Chisari FV. 2007. Double-stranded DNA and double-stranded RNA induce a common antiviral signaling pathway in human cells. Proc Natl Acad Sci U S A, 104: 9035–9040.PubMedCentralPubMedGoogle Scholar
  12. Chiu YH, Macmillan JB, Chen ZJ. 2009. RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway. Cell, 138: 576–591.PubMedCentralPubMedGoogle Scholar
  13. Cui S, Eisenacher K, Kirchhofer A, Brzozka K, Lammens A, Lammens K, Fujita T, Conzelmann KK, Krug A, Hopfner KP. 2008. The C-terminal regulatory domain is the RNA 5'-triphosphate sensor of RIG-I. Mol Cell, 29: 169–179.PubMedGoogle Scholar
  14. Daffis S, Samuel MA, Keller BC, Gale M, Jr., Diamond MS. 2007. Cell-specific IRF-3 responses protect against West Nile virus infection by interferon-dependent and-independent mechanisms. PLoS Pathog, 3: e106.PubMedCentralPubMedGoogle Scholar
  15. Daffis S, Samuel MA, Suthar MS, Keller BC, Gale M, Jr., Diamond MS. 2008. Interferon regulatory factor IRF-7 induces the antiviral alpha interferon response and protects against lethal West Nile virus infection. J Virol, 82: 8465–8475.PubMedCentralPubMedGoogle Scholar
  16. Deddouche S, Goubau D, Rehwinkel J, Chakravarty P, Begum S, Maillard PV, Borg A, Matthews N, Feng Q, van Kuppeveld J, Reis e Sousa C. 2014. Identification of an LGP2-associated MDA5 agonist in picornavirus-infected cells. Elife, 3: e01535.PubMedCentralPubMedGoogle Scholar
  17. DeWitte-Orr SJ, Collins SE, Bauer CM, Bowdish DM, Mossman KL. 2010. 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, 6: e1000829.PubMedCentralPubMedGoogle Scholar
  18. Dixit E, Boulant S, Zhang Y, Lee AS, Odendall C, Shum B, Hacohen N, Chen ZJ, Whelan SP, Fransen M, Nibert ML, Superti-Furga G, Kagan JC. 2010. Peroxisomes are signaling platforms for antiviral innate immunity. Cell, 141: 668–681.PubMedCentralPubMedGoogle Scholar
  19. Elinav E, Strowig T, Henao-Mejia J, Flavell RA. 2011. Regulation of the antimicrobial response by NLR proteins. Immunity, 34: 665–679.PubMedGoogle Scholar
  20. Errett JS, Suthar MS, McMillan A, Diamond MS, Gale M, Jr. 2013. The essential, nonredundant roles of RIG-I and MDA5 in detecting and controlling West Nile virus infection. J Virol, 87: 11416–11425.PubMedCentralPubMedGoogle Scholar
  21. Ferenci P, Scherzer TM, Kerschner H, Rutter K, Beinhardt S, Hofer H, Schoniger-Hekele M, Holzmann H, Steindl-Munda P. 2008. Silibinin is a potent antiviral agent in patients with chronic hepatitis C not responding to pegylated interferon/ribavirin therapy. Gastroenterology, 135: 1561–1567.PubMedGoogle Scholar
  22. Fredericksen BL, Keller BC, Fornek J, Katze MG, Gale M, Jr. 2008. Establishment and maintenance of the innate antiviral response to West Nile Virus involves both RIG-I and MDA5 signaling through IPS-1. J Virol, 82: 609–616.PubMedCentralPubMedGoogle Scholar
  23. Fullam A, Schroder M. 2013. DExD/H-box RNA helicases as mediators of anti-viral innate immunity and essential host factors for viral replication. Biochim Biophys Acta, 1829: 854–865.PubMedGoogle Scholar
  24. Funabiki M, Kato H, Miyachi Y, Toki H, Motegi H, Inoue M, Minowa O, Yoshida A, Deguchi K, Sato H, Ito S, Shiroishi T, Takeyasu K, Noda T, Fujita T. 2014. Autoimmune disorders associated with gain of function of the intracellular sensor MDA5. Immunity, 40: 199–212.PubMedGoogle Scholar
  25. Gao P, Ascano M, Zillinger T, Wang W, Dai P, Serganov AA, Gaffney BL, Shuman S, Jones RA, Deng L, Hartmann G, Barchet W, Tuschl T, Patel DJ. 2013. Structure-function analysis of STING activation by c[G(2',5')pA(3',5')p] and targeting by antiviral DMXAA. Cell, 154: 748–762.PubMedCentralPubMedGoogle Scholar
  26. 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. 2013. MAVS regulates apoptotic cell death by decreasing K48-linked ubiquitination of voltage-dependent anion channel 1. Mol Cell Biol, 33: 3137–3149.PubMedCentralPubMedGoogle Scholar
  27. Guarda G, Braun M, Staehli F, Tardivel A, Mattmann C, Forster I, Farlik M, Decker T, Du Pasquier RA, Romero P, Tschopp J. 2011. Type I interferon inhibits interleukin-1 production and inflammasome activation. Immunity, 34: 213–223.PubMedGoogle Scholar
  28. Hata N, Sato M, Takaoka A, Asagiri M, Tanaka N, Taniguchi T. 2001. Constitutive IFN-alpha/beta signal for efficient IFN-alpha/ beta gene induction by virus. Biochem Biophys Res Commun, 285: 518–525.PubMedGoogle Scholar
  29. Hoenen A, Liu W, Kochs G, Khromykh AA, Mackenzie JM. 2007. West Nile virus-induced cytoplasmic membrane structures provide partial protection against the interferon-induced antiviral MxA protein. J Gen Virol, 88: 3013–3017.PubMedGoogle Scholar
  30. Horner SM, Gale M, Jr. 2013. Regulation of hepatic innate immunity by hepatitis C virus. Nat Med, 19: 879–888.PubMedCentralPubMedGoogle Scholar
  31. Horner SM, Park HS, Gale M, Jr. 2012. Control of innate immune signaling and membrane targeting by the Hepatitis C virus NS3/4A protease are governed by the NS3 helix alpha0. J Virol, 86: 3112–3120.PubMedCentralPubMedGoogle Scholar
  32. Horner SM, Liu HM, Park HS, Briley J, Gale M, Jr. 2011. Mitochondrial- associated endoplasmic reticulum membranes (MAM) form innate immune synapses and are targeted by hepatitis C virus. Proc Natl Acad Sci U S A, 108: 14590–14595.PubMedCentralPubMedGoogle Scholar
  33. Hornung V, Ellegast J, Kim S, Brzozka K, Jung A, Kato H, Poeck H, Akira S, Conzelmann KK, Schlee M, Endres S, Hartmann G. 2006. 5’-Triphosphate RNA is the ligand for RIG-I. Science, 314: 994–997.PubMedGoogle Scholar
  34. Ichinohe T, Pang IK, Iwasaki A. 2010. Influenza virus activates inflammasomes via its intracellular M2 ion channel. Nat Immunol, 11: 404–410.PubMedCentralPubMedGoogle Scholar
  35. Isaacs A, Burke DC, Fadeeva L. 1958. Effect of interferon on the growth of viruses on the chick chorion. Br J Exp Pathol, 39: 447–451.PubMedCentralPubMedGoogle Scholar
  36. Iwasaki A, Medzhitov R. 2010. Regulation of adaptive immunity by the innate immune system. Science, 327: 291–295.PubMedCentralPubMedGoogle Scholar
  37. Jiang F, Ramanathan A, Miller MT, Tang GQ, Gale M, Jr., Patel SS, Marcotrigiano J. 2011. Structural basis of RNA recognition and activation by innate immune receptor RIG-I. Nature, 479: 423–427.PubMedCentralPubMedGoogle Scholar
  38. Kasturi SP, Skountzou I, Albrecht RA, Koutsonanos D, Hua T, Nakaya HI, Ravindran R, Stewart S, Alam M, Kwissa M, Villinger F, Murthy N, Steel J, Jacob J, Hogan RJ, Garcia-Sastre A, Compans R, Pulendran B. 2011. Programming the magnitude and persistence of antibody responses with innate immunity. Nature, 470: 543–547.PubMedCentralPubMedGoogle Scholar
  39. Kato H, Takeuchi O, Mikamo-Satoh E, Hirai R, Kawai T, Matsushita K, Hiiragi A, Dermody TS, Fujita T, Akira S. 2008. Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation- associated gene 5. J Exp Med, 205: 1601–1610.PubMedCentralPubMedGoogle Scholar
  40. Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, Matsui K, Uematsu S, Jung A, Kawai T, Ishii KJ, Yamaguchi O, Otsu K, Tsujimura T, Koh CS, Reise Sousa C, Matsuura Y, Fujita T, Akira S. 2006. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature, 441: 101–105.PubMedGoogle Scholar
  41. Keller BC, Fredericksen BL, Samuel MA, Mock RE, Mason PW, Diamond MS, Gale M, Jr. 2006. Resistance to alpha/beta interferon is a determinant of West Nile virus replication fitness and virulence. J Virol, 80: 9424–9434.PubMedCentralPubMedGoogle Scholar
  42. Lange CM, Jacobson IM, Rice CM, Zeuzem S. 2013. Emerging therapies for the treatment of hepatitis C. EMBO Mol Med, 6: 4–15.PubMedCentralGoogle Scholar
  43. Laurent-Rolle M, Boer EF, Lubick KJ, Wolfinbarger JB, Carmody AB, Rockx B, Liu W, Ashour J, Shupert WL, Holbrook MR, Barrett AD, Mason PW, Bloom ME, Garcia-Sastre A, Khromykh AA, Best SM. 2010. The NS5 protein of the virulent West Nile virus NY99 strain is a potent antagonist of type I interferon- mediated JAK-STAT signaling. J Virol, 84: 3503–3515.PubMedCentralPubMedGoogle Scholar
  44. Lazear HM, Pinto AK, Ramos HJ, Vick SC, Shrestha B, Suthar MS, Gale M, Jr., Diamond MS. 2013. Pattern recognition receptor MDA5 modulates CD8+ T cell-dependent clearance of West Nile virus from the central nervous system. J Virol, 87: 11401–11415.PubMedCentralPubMedGoogle Scholar
  45. Li X, Shu C, Yi G, Chaton CT, Shelton CL, Diao J, Zuo X, Kao CC, Herr AB, Li P. 2013. Cyclic GMP-AMP synthase is activated by double-stranded DNA-induced oligomerization. Immunity, 39: 1019–1031.PubMedGoogle Scholar
  46. Liu HM, Loo YM, Horner SM, Zornetzer GA, Katze MG, Gale M, Jr. 2012. The mitochondrial targeting chaperone 14-3-3epsilon regulates a RIG-I translocon that mediates membrane association and innate antiviral immunity. Cell Host Microbe, 11: 528–537.PubMedCentralPubMedGoogle Scholar
  47. Longhi MP, Trumpfheller C, Idoyaga J, Caskey M, Matos I, Kluger C, Salazar AM, Colonna M, Steinman RM. 2009. Dendritic cells require a systemic type I interferon response to mature and induce CD4+ Th1 immunity with poly IC as adjuvant. J Exp Med, 206: 1589–1602.PubMedCentralPubMedGoogle Scholar
  48. Loo YM, Fornek J, Crochet N, Bajwa G, Perwitasari O, Martinez-Sobrido L, Akira S, Gill MA, Garcia-Sastre A, Katze MG, Gale M, Jr. 2008. Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity. J Virol, 82: 335–345.PubMedCentralPubMedGoogle Scholar
  49. Loo YM, Gale M, Jr. 2011. Immune signaling by RIG-I-like receptors. Immunity, 34: 680–692.PubMedCentralPubMedGoogle Scholar
  50. Loo YM, Owen DM, Li K, Erickson AK, Johnson CL, Fish PM, Carney DS, Wang T, Ishida H, Yoneyama M, Fujita T, Saito T, Lee WM, Hagedorn CH, Lau DT, Weinman SA, Lemon SM, Gale M, Jr. 2006. Viral and therapeutic control of IFN-beta promoter stimulator 1 during hepatitis C virus infection. In: Proc Natl Acad Sci U S A, 103: 6001–6006.PubMedCentralPubMedGoogle Scholar
  51. Malathi K, Dong B, Gale M, Jr., Silverman RH. 2007. Small self- RNA generated by RNase L amplifies antiviral innate immunity. Nature, 448: 816–819.PubMedCentralPubMedGoogle Scholar
  52. Malathi K, Saito T, Crochet N, Barton DJ, Gale M, Jr., Silverman RH. 2010. RNase L releases a small RNA from HCV RNA that refolds into a potent PAMP. Rna, 16: 2108–2119.PubMedCentralPubMedGoogle Scholar
  53. Marques JT, Devosse T, Wang D, Zamanian-Daryoush M, Serbinowski P, Hartmann R, Fujita T, Behlke MA, Williams BR. 2006. A structural basis for discriminating between self and nonself double-stranded RNAs in mammalian cells. Nat Biotechnol, 24: 559–565.PubMedGoogle Scholar
  54. McCartney S, Vermi W, Gilfillan S, Cella M, Murphy TL, Schreiber RD, Murphy KM, Colonna M. 2009. Distinct and complementary functions of MDA5 and TLR3 in poly(I:C)-mediated activation of mouse NK cells. J Exp Med, 206: 2967–2976.PubMedCentralPubMedGoogle Scholar
  55. McCartney SA, Thackray LB, Gitlin L, Gilfillan S, Virgin HW, Colonna M. 2008. MDA-5 recognition of a murine norovirus. PLoS Pathog, 4: e1000108.Google Scholar
  56. Meylan E, Curran J, Hofmann K, Moradpour D, Binder M, Bartenschlager R, Tschopp J. 2005. Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature, 437: 1167–1172.PubMedGoogle Scholar
  57. Mibayashi M, Martinez-Sobrido L, Loo YM, Cardenas WB, Gale M, Jr., Garcia-Sastre A. 2007. Inhibition of retinoic acid-inducible gene I-mediated induction of beta interferon by the NS1 protein of influenza A virus. J Virol, 81: 514–524.PubMedCentralPubMedGoogle Scholar
  58. Miyashita M, Oshiumi H, Matsumoto M, Seya T. 2011. DDX60, a DEXD/H box helicase, is a novel antiviral factor promoting RIG-I-like receptor-mediated signaling. Mol Cell Biol, 31: 3802–3819.PubMedCentralPubMedGoogle Scholar
  59. Moriyama M, Kato N, Otsuka M, Shao RX, Taniguchi H, Kawabe T, Omata M. 2007. Interferon-beta is activated by hepatitis C virus NS5B and inhibited by NS4A, NS4B, and NS5A. Hepatol Int, 1: 302–310.PubMedCentralPubMedGoogle Scholar
  60. Myong S, Cui S, Cornish PV, Kirchhofer A, Gack MU, Jung JU, Hopfner KP, Ha T. 2009. Cytosolic viral sensor RIG-I is a 5'-triphosphat-dependent translocase on double-stranded RNA. Science, 323: 1070–1074.PubMedCentralPubMedGoogle Scholar
  61. Negishi H, Yanai H, Nakajima A, Koshiba R, Atarashi K, Matsuda A, Matsuki K, Miki S, Doi T, Aderem A, Nishio J, Smale ST, Honda K, Taniguchi T. 2012. Cross-interference of RLR and TLR signaling pathways modulates antibacterial T cell responses. Nat Immunol, 13: 659–666.PubMedGoogle Scholar
  62. Nikonov A, Molder T, Sikut R, Kiiver K, Mannik A, Toots U, Lulla A, Lulla V, Utt A, Merits A, Ustav M. 2013. RIG-I and MDA-5 detection of viral RNA-dependent RNA polymerase activity restricts positive-strand RNA virus replication. PLoS Pathog, 9: e1003610.PubMedCentralPubMedGoogle Scholar
  63. Onomoto K, Jogi M, Yoo JS, Narita R, Morimoto S, Takemura A, Sambhara S, Kawaguchi A, Osari S, Nagata K, Matsumiya T, Namiki H, Yoneyama M, Fujita T. 2012. Critical role of an antiviral stress granule containing RIG-I and PKR in viral detection and innate immunity. PLoS One, 7: e43031.PubMedCentralPubMedGoogle Scholar
  64. Oshiumi H, Sakai K, Matsumoto M, Seya T. 2010. DEAD/H BOX 3 (DDX3) helicase binds the RIG-I adaptor IPS-1 to up-regulate IFN-beta-inducing potential. Eur J Immunol, 40: 940–948.PubMedGoogle Scholar
  65. Parisien JP, Bamming D, Komuro A, Ramachandran A, Rodriguez JJ, Barber G, Wojahn RD, Horvath CM. 2009. A shared interface mediates paramyxovirus interference with antiviral RNA helicases MDA5 and LGP2. J Virol, 83: 7252–7260.PubMedCentralPubMedGoogle Scholar
  66. Peisley A, Lin C, Wu B, Orme-Johnson M, Liu M, Walz T, Hur S. 2011. Cooperative assembly and dynamic disassembly of MDA5 filaments for viral dsRNA recognition. Proc Natl Acad Sci U S A, 108: 21010–21015.PubMedCentralPubMedGoogle Scholar
  67. Pichlmair A, Schulz O, Tan CP, Rehwinkel J, Kato H, Takeuchi O, Akira S, Way M, Schiavo G, Reis e Sousa C. 2009. Activation of MDA5 requires higher-order RNA structures generated during virus infection. J Virol, 83: 10761–10769.PubMedCentralPubMedGoogle Scholar
  68. Poeck H, Bscheider M, Gross O, Finger K, Roth S, Rebsamen M, Hannesschlager N, Schlee M, Rothenfusser S, Barchet W, Kato H, Akira S, Inoue S, Endres S, Peschel C, Hartmann G, Hornung V, Ruland J. 2010. Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1 beta production. Nat Immunol, 11: 63–69.PubMedGoogle Scholar
  69. Ramos HJ, Lanteri MC, Blahnik G, Negash A, Suthar MS, Brassil MM, Sodhi K, Treuting PM, Busch MP, Norris PJ, Gale M, Jr. 2012. IL-1beta signaling promotes CNS-intrinsic immune control of West Nile virus infection. PLoS Pathog, 8: e1003039.PubMedCentralPubMedGoogle Scholar
  70. Runge S, Sparrer KM, Lassig C, Hembach K, Baum A, Garcia-Sastre A, Soding J, Conzelmann KK, Hopfner KP. 2014. In Vivo Ligands of MDA5 and RIG-I in Measles Virus-Infected Cells. PLoS Pathog, 10: e1004081.PubMedCentralPubMedGoogle Scholar
  71. Saito T, Hirai R, Loo YM, Owen D, Johnson CL, Sinha SC, Akira S, Fujita T, Gale M, Jr. 2007. Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2. Proc Natl Acad Sci U S A, 104: 582–587.PubMedCentralPubMedGoogle Scholar
  72. Saito T, Owen DM, Jiang F, Marcotrigiano J, Gale M, Jr. 2008. Innate immunity induced by composition-dependent RIG-I recognition of hepatitis C virus RNA. Nature, 454: 523–527.PubMedCentralPubMedGoogle Scholar
  73. Schlee M, Roth A, Hornung V, Hagmann CA, Wimmenauer V, Barchet W, Coch C, Janke M, Mihailovic A, Wardle G, Juranek S, Kato H, Kawai T, Poeck H, Fitzgerald KA, Takeuchi O, Akira S, Tuschl T, Latz E, Ludwig J, Hartmann G. 2009. Recognition of 5' triphosphate by RIG-I helicase requires short blunt double- stranded RNA as contained in panhandle of negative-strand virus. Immunity, 31: 25–34.PubMedCentralPubMedGoogle Scholar
  74. Schnell G, Loo YM, Marcotrigiano J, Gale M, Jr. 2012. Uridine composition of the poly-U/UC tract of HCV RNA defines nonself recognition by RIG-I. PLoS Pathog, 8: e1002839.PubMedCentralPubMedGoogle Scholar
  75. Schoggins JW, MacDuff DA, Imanaka N, Gainey MD, Shrestha B, Eitson JL, Mar KB, Richardson RB, Ratushny AV, Litvak V, Dabelic R, Manicassamy B, Aitchison JD, Aderem A, Elliott RM, Garcia-Sastre A, Racaniello V, Snijder EJ, Yokoyama WM, Diamond MS, Virgin HW, Rice CM. 2014. Pan-viral specificity of IFN-induced genes reveals new roles for cGAS in innate immunity. Nature, 505: 691–695.PubMedCentralPubMedGoogle Scholar
  76. Schroder K, Tschopp J. 2010. The inflammasomes. Cell, 140: 821–832.PubMedGoogle Scholar
  77. Sen GC. 2000. Novel functions of interferon-induced proteins. Semin Cancer Biol, 10: 93–101.PubMedGoogle Scholar
  78. Seth RB, Sun L, Ea CK, Chen ZJ. 2005. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell, 122: 669–682.PubMedGoogle Scholar
  79. Shigemoto T, Kageyama M, Hirai R, Zheng J, Yoneyama M, Fujita T. 2009. Identification of loss of function mutations in human genes encoding RIG-I and MDA5: implications for resistance to type I diabetes. J Biol Chem, 284: 13348–13354.PubMedCentralPubMedGoogle Scholar
  80. Stoddard MB, Li H, Wang S, Saeed M, Andrus L, Ding W, Jiang X, Learn GH, von Schaewen M, Wen J, Goepfert PA, Hahn BH, Ploss A, Rice CM, Shaw GM. 2015. Identification, molecular cloning, and analysis of full-length hepatitis C virus transmitted/ founder genotypes 1, 3, and 4. MBio, 6: e02518.PubMedCentralPubMedGoogle Scholar
  81. Subramanian N, Natarajan K, Clatworthy MR, Wang Z, Germain RN. 2013. The adaptor MAVS promotes NLRP3 mitochondrial localization and inflammasome activation. Cell, 153: 348–361.PubMedCentralPubMedGoogle Scholar
  82. Sun L, Wu J, Du F, Chen X, Chen ZJ. 2013. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science, 339: 786–791.PubMedGoogle Scholar
  83. Suthar MS, Diamond MS, Gale M, Jr. 2013. West Nile virus infection and immunity. Nat Rev Microbiol, 11: 115–128.PubMedGoogle Scholar
  84. Suthar MS, Ma DY, Thomas S, Lund JM, Zhang N, Daffis S, Rudensky AY, Bevan MJ, Clark EA, Kaja MK, Diamond MS, Gale M, Jr. 2010. IPS-1 is essential for the control of West Nile virus infection and immunity. PLoS Pathog, 6: e1000757.PubMedCentralPubMedGoogle Scholar
  85. Suthar MS, Ramos HJ, Brassil MM, Netland J, Chappell CP, Blahnik G, McMillan A, Diamond MS, Clark EA, Bevan MJ, Gale M, Jr. 2012. The RIG-I-like Receptor LGP2 Controls CD8(+) T Cell Survival and Fitness. Immunity, 37: 235–248.PubMedCentralPubMedGoogle Scholar
  86. Takahasi K, Kumeta H, Tsuduki N, Narita R, Shigemoto T, Hirai R, Yoneyama M, Horiuchi M, Ogura K, Fujita T, Inagaki F. 2009. Solution structures of cytosolic RNA sensor MDA5 and LGP2 C-terminal domains: identification of the RNA recognition loop in RIG-I-like receptors. J Biol Chem, 284: 17465–17474.PubMedCentralPubMedGoogle Scholar
  87. Takahasi K, Yoneyama M, Nishihori T, Hirai R, Kumeta H, Narita R, Gale M, Jr., Inagaki F, Fujita T. 2008. Nonself RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses. Mol Cell, 29: 428–440.PubMedGoogle Scholar
  88. Takeda K, Akira S. 2004. TLR signaling pathways. Semin Immunol, 16: 3–9.PubMedGoogle Scholar
  89. Takeuchi O, Akira S. 2008. MDA5/RIG-I and virus recognition. Curr Opin Immunol, 20: 17–22.PubMedGoogle Scholar
  90. Venkataraman T, Valdes M, Elsby R, Kakuta S, Caceres G, Saijo S, Iwakura Y, Barber GN. 2007. Loss of DExD/H box RNA helicase LGP2 manifests disparate antiviral responses. J Immunol, 178: 6444–6455.PubMedGoogle Scholar
  91. Wang Y, Cella M, Gilfillan S, Colonna M. 2010. 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, 184: 2751–2755.PubMedGoogle Scholar
  92. Williams BR. 2001. Signal integration via PKR. Sci STKE, 2001. re2.Google Scholar
  93. Wu J, Chen ZJ. 2014. Innate immune sensing and signaling of cytosolic nucleic acids. Annu Rev Immunol, 32: 461–488.PubMedGoogle Scholar
  94. Wu J, Sun L, Chen X, Du F, Shi H, Chen C, Chen ZJ. 2013. Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science, 339: 826–830.PubMedGoogle Scholar
  95. Xu LG, Wang YY, Han KJ, Li LY, Zhai Z, Shu HB. 2005. VISA is an adapter protein required for virus-triggered IFN-beta signaling. Mol Cell, 19: 727–740.PubMedGoogle Scholar
  96. Yanai H, Ban T, Wang Z, Choi MK, Kawamura T, Negishi H, Nakasato M, Lu Y, Hangai S, Koshiba R, Savitsky D, Ronfani L, Akira S, Bianchi ME, Honda K, Tamura T, Kodama T, Taniguchi T. 2009. HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses. Nature, 462: 99–103.PubMedGoogle Scholar
  97. Yedavalli VS, Neuveut C, Chi YH, Kleiman L, Jeang KT. 2004. Requirement of DDX3 DEAD box RNA helicase for HIV-1 Rev-RRE export function. Cell, 119: 381–392.PubMedGoogle Scholar
  98. Yoo JS, Takahasi K, Ng CS, Ouda R, Onomoto K, Yoneyama M, Lai JC, Lattmann S, Nagamine Y, Matsui T, Iwabuchi K, Kato H, Fujita T. 2014. DHX36 enhances RIG-I signaling by facilitating PKR-mediated antiviral stress granule formation. PLoS Pathog, 10: e1004012.PubMedCentralPubMedGoogle Scholar
  99. You F, Wang P, Yang L, Yang G, Zhao YO, Qian F, Walker W, Sutton R, Montgomery R, Lin R, Iwasaki A, Fikrig E. 2013. ELF4 is critical for induction of type I interferon and the host antiviral response. Nat Immunol, 14: 1237–1246.PubMedCentralPubMedGoogle Scholar
  100. Yount JS, Moran TM, Lopez CB. 2007. Cytokine-independent upregulation of MDA5 in viral infection. J Virol, 81: 7316–7319.PubMedCentralPubMedGoogle Scholar
  101. Zhang X, Shi H, Wu J, Sun L, Chen C, Chen ZJ. 2013. Cyclic GMPAMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING. Mol Cell, 51: 226–235.PubMedGoogle Scholar
  102. Zhang Z, Yuan B, Lu N, Facchinetti V, Liu YJ. 2011. DHX9 pairs with IPS-1 to sense double-stranded RNA in myeloid dendritic cells. J Immunol, 187: 4501–4508.PubMedCentralPubMedGoogle Scholar
  103. Zhou S, Cerny AM, Zacharia A, Fitzgerald KA, Kurt-Jones EA, Finberg RW. 2010. Induction and inhibition of type I interferon responses by distinct components of lymphocytic choriomeningitis virus. J Virol, 84: 9452–9462.PubMedCentralPubMedGoogle Scholar
  104. Zust R, Cervantes-Barragan L, Habjan M, Maier R, Neuman BW, Ziebuhr J, Szretter KJ, Baker SC, Barchet W, Diamond MS, Siddell SG, Ludewig B, Thiel V. 2011. 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 12: 137–143.PubMedCentralPubMedGoogle Scholar

Copyright information

© Wuhan Institute of Virology, CAS and Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Center for Innate Immunity and Immune Disease, Department of Immunology, School of MedicineUniversity of WashingtonSeattleUSA

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