Abstract

One of the key determinants of survival for organisms is proper recognition of exogenous and endogenous nucleic acids. Therefore, high eukaryotes developed a number of receptors that allow for discrimination between friend or foe DNA and RNA. Appearance of exogenous RNA in cytoplasm provides a signal of danger and triggers cellular responses that facilitate eradication of a pathogen. Recognition of exogenous RNA is additionally complicated by fact that large amount of endogenous RNA is present in cytoplasm Thus, number of different receptors, found in eukaryotic cells, is able to recognize that nucleic acid. First group of those receptors consist endosomal Toll like receptors, namely TLR3, TLR7, TLR8 and TLR13. Those receptors recognize RNA released from pathogens that enter the cell by endocytosis. The second group includes cytoplasmic sensors like PKR and the family of RLRs comprised of RIG-I, MDA5 and LGP2. Cytoplasmic receptors recognize RNA from pathogens invading the cell by non-endocytic pathway. In both cases binding of RNA by its receptors results in activation of the signalling cascades that lead to the production of interferon and other cytokines.

References

• 1. Akira S., Hemmi H.: Recognition of pathogen-associated molecularpatterns by TLR family. Immunol. Lett., 2003; 85: 85-95
  Google Scholar
• 2. Alexopoulou L., Holt A.C., Medzhitov R., Flavell R.A.: Recognition ofdouble-stranded RNA and activation of NF-κB by Toll-like receptor 3.Nature, 2001; 413: 732-738
  Google Scholar
• 3. Baccarella A., Fontana M.F., Chen E.C., Kim C.C.: Toll-like receptor 7mediates early innate immune responses to malaria. Infect. Immun.,2013; 81: 4431-4442
  Google Scholar
• 4. Bao M., Liu Y.J.: Regulation of TLR7/9 signaling in plasmacytoid dendriticcells. Protein Cell, 2013; 4: 40-52
  Google Scholar
• 5. Barral P.M., Sarkar D., Su Z.Z., Barber G.N., DeSalle R., RacanielloV.R., Fisher P.B.: Functions of the cytoplasmic RNA sensors RIG-I andMDA-5: key regulators of innate immunity. Pharmacol. Toxicol., 2009;124: 219-234
  Google Scholar
• 6. Bauer S., Pigisch S., Hangel D., Kaufmann A., Hamm S.: Recognitionof nucleic acid and nucleic acid analogs by Toll-like receptors 7, 8 and 9 Immunobiol., 2008; 213: 315-328
  Google Scholar
• 7. Baum A., Sachidanandam R., Garcia-Sastre A.: Preference of RIG-I forshort viral RNA molecules in infected cells revealed by next-generationsequencing. Proc. Natl. Acad. Sci. USA, 2010; 107: 16303-16308
  Google Scholar
• 8. Beignon A.S., McKenna K., Skoberne M., Manches O., DaSilva I., KavanaghD.G., Larsson M., Gorelick R.J., Lifson J.D., Bhardwaj N.: Endocytosisof HIV-1 activates plasmacytoid dendritic cells via Toll-like receptorviralRNA interactions. J. Clin. Invest., 2005; 115: 3265-3275
  Google Scholar
• 9. Berg R.K., Melchjorsen J., Rintahaka J., Diget E., Soby S., Horan K.A.,Gorelick R.J., Matikainen S., Larsen C.S., Ostergaard L., Paludan S.R.,Mogensen T.H.: Genomic HIV RNA induces innate immune responsesthrough RIG-I-dependent sensing of secondary-structured RNA. PloSOne, 2012; 7: e29291
  Google Scholar
• 10. Berke I.C., Li Y., Modis Y.: Structural basis of innate immune recognitionof viral RNA. Cell. Microbiol., 2013; 15: 386-394
  Google Scholar
• 11. Bianchi M.E.: DAMPs, PAMPs and alarmins: all we need to knowabout danger. J. Leukoc. Biol., 2007; 81: 1-5
  Google Scholar
• 12. Cardenas W.B., Loo Y.M., Gale M. Jr., Hartman A.L., Kimberlin C.R.,Martinez-Sobrido L., Saphire E.O, Basler C.F.: Ebola virus VP35 proteinbinds double-stranded RNA and inhibits a/b interferon production inducedby RIG-I signaling. J. Virol., 2006; 80: 5168-5178
  Google Scholar
• 13. Cervantes J.L., Weinerman B., Basole C., Salazar J.C.: TLR8: the forgottenrelative revindicated. Cell. Mol. Immunol., 2012; 9: 434-438
  Google Scholar
• 14. Childs K.S., Randall R.E., Goodbourn S.: LGP2 plays a critical rolein sensitizing mda-5 to activation by double-stranded RNA. PloS One,2013; 8: e64202
  Google Scholar
• 15. Choe J., Kelker M.S., Wilson I.A.: Crystal structure of human Toll-likereceptor 3 (TLR3) ectodomain. Science, 2005; 309: 581-585
  Google Scholar
• 16. Cole J.L.: Activation of PKR: an open and shut case? Trends Biochem.Sci., 2007; 32: 57-62
  Google Scholar
• 17. Creagh E.M., O’Neill L.A.J.: TLRs, NLRs and RLRs: a trinity of pathogensensors that co-operate in innate immunity. Trends Immunol.,2006; 27: 352-357
  Google Scholar
• 18. Deddouche S., Goubau D., Rehwinkel J., Chakravarty P., Begum S.,Maillard P.V., Borg A., Matthews N., Feng Q., van Kuppeveld F.J., Reis eSousa C.: Identification of an LGP2-associated MDA5 agonist in picornavirus-infected cells. Elife, 2014; 3: e01535
  Google Scholar
• 19. Diebold S.S., Kaisho T., Hemmi H., Akira S., Reis e Sousa C.R: Innateantiviral responses by means of TLR7-mediated recognition of singlestrandedRNA. Science, 2004; 303: 1529-1531
  Google Scholar
• 20. Dixit E., Boulant S., Zhang Y., Lee A.S., Odendall C., Shum B., HacohenN., Chen Z.J., Whelan S.P., Fransen M., Nibert M.L., Superti-FurgaG., Kagan J.C.: Peroxisomes are signaling platforms for antiviral innateimmunity. Cell, 2010; 141: 668-681
  Google Scholar
• 21. Gack M.U., Albrecht R.A., Urano T., Inn K-S., Huang I.C., Carnero E.,Farzan M., Inoue S., Jung J.U., García-Sastre A.: Influenza A virus NS1targets the ubiquitin ligase TRIM25 to evade recognition by the hostviral RNA sensor RIG-I. Cell Host Microbe, 2009; 5: 439-449
  Google Scholar
• 22. Gack M.U., Shin Y.C., Joo C.H., Urano T., Liang C., Sun L., TakeuchiO., Akira S., Chen Z., Inoue S., Jung J.U.: TRIM25 RING-finger E3 ubiquitinligase is essential for RIG-I-mediated antiviral activity. Nature,2007; 446: 916-920
  Google Scholar
• 23. Gantier M.P., Tong S., Behlke M.A., Xu D., Phipps S., Foster P.S.,Williams B.R.: TLR7 is involved in sequence-specific sensing of singlestrandedRNAs in human macrophages. J. Immunol., 2008; 180: 2117-2124
  Google Scholar
• 24. Gitlin L., Barchet W., Gilfillan S., Cella M., Beutler B., Flavell R.A., DiamondM.S., Colonna M.: Essential role of mda-5 in type I IFN responsesto polyriboinosinic: polyribocytidylic acid and encephalomyocarditispicornavirus. Proc. Natl. Acad. Sci. USA, 2006; 103: 8459-8464
  Google Scholar
• 25. Gorden K.B., Gorski K.S., Gibson S.J., Kedl R.M., Kieper W.C., QiuX.H., Tomai M.A., Alkan S.S., Vasilakos J.P.: Synthetic TLR agonists revealfunctional differences between human TLR7 and TLR8. J. Immunol.,2005; 174: 1259-1268
  Google Scholar
• 26. Goubau D., Deddouche S., Reis e Sousa C.: Cytosolic sensing of viruses.Immunity, 2013; 38: 855-869
  Google Scholar
• 27. Goubau D., Schlee M., Deddouche S., Pruijssers A.J., Zillinger T.,Goldeck M., Schuberth C., Van der Veen A.G., Fujimura T., RehwinkelJ., Iskarpatyoti J.A., Barchet W., Ludwig J., Dermody T.S., Hartmann G.,Reis e Sousa C.: Antiviral immunity via RIG-I-mediated recognition ofRNA bearing 5 ‚-diphosphates. Nature, 2014; 514: 372-375
  Google Scholar
• 28. Guillot L., Le Goffic R., Bloch S., Escriou N., Akira S., Chignard M., Si-Tahar M.: Involvement of toll-like receptor 3 in the immune responseof lung epithelial cells to double-stranded RNA and influenza A virus.J. Biol. Chem., 2005; 280: 5571-5580
  Google Scholar
• 29. Hornung V., Ablasser A., Charrel-Dennis M., Bauernfeind F., HorvathG., Caffrey D.R., Latz E., Fitzgerald K.A.: AIM2 recognizes cytosolicdsDNA and forms a caspase-1-activating inflammasome with ASC. Nature,2009; 458: 514-518
  Google Scholar
• 30. Hornung V., Rothenfusser S., Britsch S., Krug A., Jahrsdorfer B.,Giese T., Endres S., Hartmann G.: Quantitative expression of Toll-likereceptor 1-10 mRNA in cellular subsets of human peripheral bloodmononuclear cells and sensitivity to CpG oligodeoxynucleotides. J. Immunol.,2002; 168: 4531-4537
  Google Scholar
• 31. Jin M.S., Lee J.O.: Structures of the toll-like receptor family and itsligand complexes. Immunity., 2008; 29: 182-191
  Google Scholar
• 32. Jurk M., Heil F., Vollmer J., Schetter C., Krieg A.M., Wagner H., LipfordG., Bauer S.: Human TLR7 or TLR8 independently confer responsivenessto the antiviral compound R-848. Nat. Immunol., 2002; 3: 499
  Google Scholar
• 33. Jurk M., Kritzler A., Schulte B., Tluk S., Schetter C., Krieg AM.,Vollmer J.: Modulating responsiveness of human TLR7 and 8 to smallmolecule ligands with T-rich phosphorothiate oligodeoxynucleotides.Eur. J. Immunol., 2006; 36: 1815-1826
  Google Scholar
• 34. Kang D.C., Gopalkrishnan R.V., Lin L., Randolph A., Valerie K., PestkaS., Fisher P.B.: Expression analysis and genomic characterization of humanmelanoma differentiation associated gene-5, mda-5: a novel typeI interferon-responsive apoptosis-inducing gene. Oncogene, 2004; 23:1789-1800
  Google Scholar
• 35. Kang J.I., Kwon S.N., Park S.H., Kim Y.K., Choi S.Y., Kim J.P., Ahn B.Y.:PKR protein kinase is activated by hepatitis C virus and inhibits viralreplication through translational control. Virus Res., 2009; 142: 51-56
  Google Scholar
• 36. Kato H., Takeuchi O., Mikamo-Satoh E., Hirai R., Kawai T., MatsushitaK., Hiiragi A., Dermody T.S., Fujita T., Akira S.: Length-dependent recognitionof double-stranded ribonucleic acids by retinoic acid-induciblegene-I and melanoma differentiation-associated gene 5. J. Exp. Med.,2008; 205: 1601-1610
  Google Scholar
• 37. Kato H., Takeuchi O., Sato S., Yoneyama M., Yamamoto M., MatsuiK., Uematsu S., Jung A., Kawai T., Ishii K.J., Yamaguchi O., Otsu K., TsujimuraT., Koh C.S., Reis e Sousa C., Matsuura Y., Fujita T., Akira S.: Differential roles of MDA5 and RIG-I helicases in the recognition of RNAviruses. Nature, 2006; 441: 101-105
  Google Scholar
• 38. Kawai T., Akira S.: The roles of TLRs, RLRs and NLRs in pathogenrecognition. Int. Immunol., 2009; 21: 317-337
  Google Scholar
• 39. Kowalinski E., Lunardi T., McCarthy A.A., Louber J., Brunel J., GrigorovB., Gerlier D., Cusack S.: Structural basis for the activation of innateimmune pattern-recognition receptor RIG-I by viral RNA. Cell,2011; 147: 423-435
  Google Scholar
• 40. Koyama S., Ishii K.J., Kumar H., Tanimoto T., Coban C., Uematsu S.,Kawai T., Akira S.: Differential role of TLR – and RLR-signaling in theimmune responses to influenza a virus infection and vaccination. J.Immunol., 2007; 179: 4711-4720
  Google Scholar
• 41. Lafon M., Megret F., Lafage M., Prehaud C.: The innate immune facetof brain – human neurons express TLR-3 and sense viral dsRNA. J. Mol.Neurosci., 2006; 29: 185-194
  Google Scholar
• 42. Ling Z., Tran K.C., Teng M.N.: Human respiratory syncytial virusnonstructural protein NS2 antagonizes the activation of beta interferontranscription by interacting with RIG-I. J. Virol., 2009; 83: 3734-3742
  Google Scholar
• 43. Liu L., Botos I., Wang Y., Leonard J.N., Shiloach J., Segal D.M., DaviesD.R.: Structural basis of toll-like receptor 3 signaling with doublestrandedRNA. Science, 2008; 320: 379-381
  Google Scholar
• 44. Liu X., Bennett R.L., Cheng X., Byrne M., Reinhard M.K., May W.S.Jr.:PKR regulates proliferation, differentiation, and survival of murine hematopoieticstem/progenitor cells. Blood, 2013; 121: 3364-3374
  Google Scholar
• 45. 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., Gale M. Jr.:Distinct RIG-I and MDA5 signaling regulation by RNA viruses in innateimmunity. J. Virol., 2008; 82: 335-345
  Google Scholar
• 46. Loo Y.M., Gale M. Jr.: Immune signaling by RIG-I-like receptors. Immunity,2011; 34: 680-692
  Google Scholar
• 47. Luo D., Ding S.C., Vela A., Kohlway A., Lindenbach B.D., Pyle A.M.:Structural insights into RNA recognition by RIG-I. Cell, 2011; 147: 409-422
  Google Scholar
• 48. Maharaj N.P., Wies E., Stoll A., Gack M.U.: Conventional protein kinaseC-α (PKC-α) and PKC-β negatively regulate RIG-I antiviral signaltransduction. J. Virol., 2012; 86: 1358-1371
  Google Scholar
• 49. Marcotrigiano J., Gingras A.C., Sonenberg N., Burley S.K.: Cocrystalstructure of the messenger RNA 5› cap-binding protein (eIF4E) boundto 7-methyl-GDP. Cell, 1997; 89: 951-961
  Google Scholar
• 50. Marsh M., Helenius A.: Virus entry: open sesame. Cell, 2006; 124:729-740
  Google Scholar
• 51. Matsumoto M., Kikkawa S., Kohase M., Miyake K., Seya T.: Establishmentof a monoclonal antibody against human Toll-like receptor 3 thatblocks double-stranded RNA-mediated signaling. Biochem. Biophys.Res. Commun., 2002; 293: 1364-1369
  Google Scholar
• 52. Matsumoto M., Seya T.: TLR3: Interferon induction by doublestrandedRNA including poly(I:C). Adv. Drug Deliv. Rev., 2008; 60: 805-812
  Google Scholar
• 53. Meurs E., Chong K., Galabru J., Thomas N.S., Kerr I.M., Williams B.R.,Hovanessian A.G.: Molecular cloning and characterization of the humandouble-stranded RNA-activated protein kinase induced by interferon.Cell, 1990; 62: 379-390
  Google Scholar
• 54. Meylan E., Curran J., Hofmann K., Moradpour D., Binder M.,Bartenschlager R., Tschoop J.: Cardif is an adaptor protein in the RIGIantiviral pathway and is targeted by hepatitis C virus. Nature, 2005;437: 1167-1172
  Google Scholar
• 55. Myong S., Cui S., Cornish P.V., Kirchhofer A., Gack M.U., Jung J.U.,Hopfner K.P., Ha T.: Cytosolic viral sensor RIG-I is a 5’-triphosphatedependenttranslocase on double-stranded RNA. Science, 2009; 323:1070-1074
  Google Scholar
• 56. Norden R., Nystrom K., Olofsson S.: Activation of host antiviralRNA-sensing factors necessary for herpes simplex virus type 1-activated transcription of host cell fucosyltransferase genes FUT3, FUT5,and FUT6 and subsequent expression of sLe(x) in virus-infected cells.Glycobiology, 2009; 19: 776-788
  Google Scholar
• 57. Oldenburg M., Kruger A., Ferstl R., Kaufmann A., Nees G., SigmundA., Bathke B., Lauterbach H., Suter M., Dreher S., Koedel U., Akira S.,Kawai T., Buer J., Wagner H., Bauer S., Hochrein H., Kirschning C.J.:TLR13 recognizes bacterial 23S rRNA devoid of erythromycin resistanceformingmodification. Science, 2012; 337: 1111-1115
  Google Scholar
• 58. Opitz C.A., Litzenburger U.M., Lutz C., Lanz T.V., Tritschler I., KoppelA., Tolosa E., Hoberg M., Anderl J., Aicher W.K., Weller M., Wick W.,Platten M.: Toll-like receptor engagement enhances the immunosuppressiveproperties of human bone marrow-derived mesenchymal stemcells by inducing indoleamine-2,3-dioxygenase-1 via interferon-b andprotein kinase R. Stem Cells, 2009; 27: 909-919
  Google Scholar
• 59. Paz S., Sun Q., Nakhaei P., Romieu-Mourez R., Goubau D., JulkunenI., Lin R., Hiscott J.: Induction of IRF-3 and IRF-7 phosphorylation followingactivation of the RIG-I pathway. Cell Mol. Biol., 2006; 52: 17-28
  Google Scholar
• 60. Pfaller C.K., Radeke M.J., Cattaneo R., Samuel C.E.: Measles virusC protein impairs production of defective copyback double-strandedviral RNA and activation of protein kinase R. J. Virol., 2014; 88: 456-468
  Google Scholar
• 61. Plumet S., Duprex W.P., Gerlier D.: Dynamics of viral RNA synthesisduring measles virus infection. J. Virol., 2005; 79: 6900-6908
  Google Scholar
• 62. Powers C., DeFilippis V., Malouli D., Frueh K.: Cytomegalovirus immuneevasion. Curr. Top. Microbiol. Immunol., 2008; 325: 333-359
  Google Scholar
• 63. Rehwinkel J., Tan C.P., Goubau D., Schulz O., Pichlmair A., Bier K.,Robb N., Vreede F., Barclay W., Fodor E., Reis e Sousa C.: RIG-I detectsviral genomic RNA during negative-strand RNA virus infection. Cell,2010; 140: 397-408
  Google Scholar
• 64. Rua R., Lepelley A., Gessain A., Schwartz O.: Innate sensing of foamyviruses by human hematopoietic cells. J. Virol., 2012; 86: 909-918
  Google Scholar
• 65. Runge S., Sparrer K.M., Laessig C., Hembach K., Baum A., Garcia-Sastre A., Söding J., Conzelmann K.K., Hopfner K.P.: In vivo ligands ofMDA5 and RIG-I in measles virus-infected cells. PLoS Pathog., 2014;10: e1004081
  Google Scholar
• 66. Rutz M., Metzger J., Gellert T., Luppa P., Lipford G.B., Wagner H., BauerS.: Toll-like receptor 9 binds single-stranded CpG-DNA in a sequence– and pH-dependent manner. Eur. J. Immunol., 2004; 34: 2541-2550
  Google Scholar
• 67. Sadler A.J., Williams B.R.: Structure and function of the protein kinaseR. Curr. Top. Microbiol. Immunol., 2007; 316: 253-292
  Google Scholar
• 68. Saito T., Hirai R., Loo Y.M., Owen D., Johnson C.L., Sinha S.C., AkiraS., Fujita T., Gale M. Jr: Regulation of innate antiviral defenses througha shared repressor domain in RIG-I and LGP2. Proc. Natl. Acad. Sci. USA,2007; 104: 582-587
  Google Scholar
• 69. Sarvestani S.T., Stunden H.J., Behlke M.A., Forster S.C., McCoy C.E.,Tate M.D., Ferrand J., Lennox K.A., Latz E., Williams B.R., Gantier M.P.:Sequence-dependent off-target inhibition of TLR7/8 sensing by syntheticmicroRNA inhibitors. Nucleic Acids Res., 2015; 43: 1177-1188
  Google Scholar
• 70. Satoh T., Kato H., Kumagai Y., Yoneyama M., Sato S., Matsushita K.,Tsujimura T., Fujita T., Akira S., Takeuchi O.: LGP2 is a positive regulatorof RIG-I – and MDA5-mediated antiviral responses. Proc. Natl. Acad. Sci.USA, 2010; 107: 1512-1517
  Google Scholar
• 71. Schulz O., Pichlmair A., Rehwinkel J., Rogers N.C., Scheuner D., KatoH., Takeuchi O., Akira S., Kaufman R.J., Reis e Sousa C.: Protein kinase Rcontributes to immunity against specific viruses by regulating interferonmRNA integrity. Cell Host Microbe, 2010; 7: 354-361
  Google Scholar
• 72. Sen G.C., Sarkar S.N.: Transcriptional signaling by double-strandedRNA: role of TLR3. Cytokine Growth Factor Rev., 2005; 16: 1-14
  Google Scholar
• 73. Shi Z., Cai Z., Sanchez A., Zhang T., Wen S., Wang J., Yang J., Fu S.,Zhang D.: A novel Toll-like receptor that recognizes vesicular stomatitisvirus. J. Biol. Chem., 2011; 286: 4517-4524
  Google Scholar
• 74. Signorino G., Mohammadi N., Patane F., Buscetta M., Venza M.,Venza I., Mancuso G., Midiri A., Alexopoulou L., Teti G., Biondo C., Beninati C.: Role of Toll-like receptor 13 in innate immune recognition ofgroup B streptococci. Infect. Immun., 2014; 82: 5013-5022
  Google Scholar
• 75. Silva A.M., Whitmore M., Xu Z., Jiang Z.F., Li X.X., Williams B.R.:Protein kinase R (PKR) interacts with and activates mitogen-activatedprotein kinase kinase 6 (MKK6) in response to double-stranded RNAstimulation. J. Biol. Chem., 2004; 279: 37670-37676
  Google Scholar
• 76. Sun L., Wu J., Du F., Chen X., Chen Z.J.: Cyclic GMP-AMP synthaseis a cytosolic DNA sensor that activates the type I interferon pathway.Science, 2013; 339: 786-791
  Google Scholar
• 77. Takada E., Okahira S., Sasai M., Funami K., Seya T., Matsumoto M.:C-terminal LRRs of human Toll-like receptor 3 control receptor dimerizationand signal transmission. Mol. Immunol., 2007; 44: 3633-3640
  Google Scholar
• 78. Tolle L.B., Standiford T.J.: Danger-associated molecular patterns(DAMPs) in acute lung injury. J. Pathol., 2013; 229: 145-156
  Google Scholar
• 79. Triantafilou K., Vakakis E., Orthopoulos G., Ahmed M.A., SchumannC., Lepper P.M., Triantafilou M.: TLR8 and TLR7 are involved in thehost’s immune response to human parechovirus 1. Eur. J. Immunol.,2005; 35: 2416-2423
  Google Scholar
• 80. Vercammen E., Staal J., Beyaert R.: Sensing of viral infection andactivation of innate immunity by toll-like receptor 3. Clin. Microbiol.Rev., 2008; 21: 13-25
  Google Scholar
• 81. Vijay-Kumar M., Gentsch J.R., Kaiser W.J., Borregaard N., OffermannM.K., Neish A.S., Gewirtz A.T.: Protein kinase R mediates intestinal epithelialgene remodeling in response to double-stranded RNA and liverotavirus. J. Immunol., 2005; 174: 6322-6331
  Google Scholar
• 82. Wei T., Gong J., Jamitzky F., Heckl W.M., Stark R.W., Roessle S.C.:Homology modeling of human Toll-like receptors TLR7, 8, and 9 ligandbindingdomains. Protein Sci., 2009; 18: 1684-1691
  Google Scholar
• 83. Wies E., Wang M.K., Maharaj N.P., Chen K., Zhou S., Finberg R.W.,Gack M.U.: Dephosphorylation of the RNA sensors RIG-I and MDA5 bythe phosphatase PP1 is essential for innate immune signaling. Immunity,2013; 38: 437-449
  Google Scholar
• 84. Wu B., Peisley A., Richards C., Yao H., Zeng X., Lin C., Chu F., Walz T.,Hur S.: Structural basis for dsRNA recognition, filament formation, andantiviral signal activation by MDA5. Cell, 2013; 152: 276-289
  Google Scholar
• 85. Xing J., Wang S., Lin R., Mossman K.L., Zheng C.: Herpes simplexvirus 1 tegument protein US11 downmodulates the RLR signaling pathwayvia direct interaction with RIG-I and MDA-5. J. Virol., 2012; 86:3528-3540
  Google Scholar
• 86. Xu H., He X., Zheng H., Huang L.J., Hou F., Yu Z., de la Cruz M.J.,Borkowski B., Zhang X., Chen Z.J., Jiang Q.X.: Structural basis for theprion-like MAVS filaments in antiviral innate immunity. Elife, 2014;3: e01489
  Google Scholar
• 87. Yoneyama M., Fujita T.: Structural mechanism of RNA recognitionby the RIG-l-like receptors. Immunity, 2008; 29: 178-181
  Google Scholar
• 88. Yoneyama M., Kikuchi M., Matsumoto K., Imaizumi T., MiyagishiM., Taira K., Foy E., Loo Y.M., Gale M. Jr., Akira S., Yonehara S., Kato A.,Fujita T.: Shared and unique functions of the DExD/H-box helicasesRIG-I, MDA5, and LGP2 in antiviral innate immunity. J. Immunol., 2005;175: 2851-2858
  Google Scholar
• 89. Yoneyama M., Kikuchi M., Natsukawa T., Shinobu N., Imaizumi T.,Miyagishi M., Taira K., Akira S., Fujita T.: The RNA helicase RIG-I has anessential function in double-stranded RNA-induced innate antiviralresponses. Nat. Immunol., 2004; 5: 730-737
  Google Scholar
• 90. Zucchini N., Bessou G., Traub S., Robbins S.H., Uematsu S., Akira S.,Alexopoulou L., Dalod M.: Cutting edge: Overlapping functions of TLR7and TLR9 for innate defense against a herpesvirus infection. J. Immunol.,2008; 180: 5799-5803
  Google Scholar

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