Pattern recognition and signaling mechanisms of RIG-I and MDA5

Frontiers in Immunology

Volumn 5, Issue JUL, 2014, Pages

  Reikine, Stephanie ^a   Nguyen, Jennifer B ^a   Modis, Yorgo ^a  

^a YALE UNIVERSITY   (United States)

Author keywords

Amyloid like aggregation; Caspase recruitment domain; Nucleic acid sensor; Pathogen associated molecular pattern; Prion like switch; RecA like DEAD box (DExD H box) RNA helicase; Signal transduction; Signalosome

Indexed keywords

EID: 84905661532     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2014.00342     Document Type: Short Survey

References (69)

1. Janeway CA Jr, Medzhitov R. Innate immune recognition. Annu Rev Immunol (2002) 20:197-216. doi: 10.1146/annurev.immunol.20.083001.084359
2. Vautier S, MacCallum DM, Brown GD. C-type lectin receptors and cytokines in fungal immunity. Cytokine (2012) 58(1):89-99. doi:10.1016/j.cyto.2011.08.031
3. Choi JS, Ryter SW. Inflammasomes: molecular regulation and implications for metabolic and cognitive diseases. Mol Cells (2014) 37:441-8. doi:10.14348/molcells.2014.0104
4. Ferrao R, Li J, Bergamin E, Wu H. Structural insights into the assembly of large oligomeric signalosomes in the Toll-like receptor-interleukin-1 receptor superfamily. Sci Signal (2012) 5(226):re3. doi:10.1126/scisignal.2003124
5. Ahmad-Nejad P, Hacker H, Rutz M, Bauer S, Vabulas RM, Wagner H. Bacterial CpG-DNA and lipopolysaccharides activate Toll-like receptors at distinct cellular compartments. Eur J Immunol (2002) 32(7):1958-68. doi:10.1002/1521-4141(200207)32:71958::AID-IMMU19583.0.CO;2-U
6. Matsumoto M, Funami K, Tanabe M, Oshiumi H, Shingai M, Seto Y, et al. Subcellular localization of Toll-like receptor 3 in human dendritic cells. J Immunol (2003) 171(6):3154-62. doi:10.4049/jimmunol.171.9.4934-b
7. Nishiya T, Kajita E, Miwa S, Defranco AL. TLR3 and TLR7 are targeted to the same intracellular compartments by distinct regulatory elements. J Biol Chem (2005) 280(44):37107-17. doi:10.1074/jbc.M504951200
8. Latz E, Schoenemeyer A, Visintin A, Fitzgerald KA, Monks BG, Knetter CF, et al. TLR9 signals after translocating from the ER to CpG DNA in the lysosome. Nat Immunol (2004) 5(2):190-8. doi:10.1038/ni1028
9. Rigby RE, Webb LM, Mackenzie KJ, Li Y, Leitch A, Reijns MA, et al. RNA:DNA hybrids are a novel molecular pattern sensed by TLR9. EMBO J (2014) 33(6):542-58. doi:10.1002/embj.201386117
10. 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(7089):101-5. doi:10.1038/nature04734
11. Hornung V, Ellegast J, Kim S, Brzozka K, Jung A, Kato H, et al. 5'-Triphosphate RNA is the ligand for RIG-I. Science (2006) 314:994-7. doi:10.1126/science.1132505
12. Pichlmair A, Schulz O, Tan CP, Naslund TI, Liljestrom P, Weber F, et al. RIG-I-mediated antiviral responses to single-stranded RNA bearing 5' phosphates. Science (2006) 314:997-1001. doi:10.1126/science.1132998
13. Holm CK, Paludan SR, Fitzgerald KA. DNA recognition in immunity and disease. Curr Opin Immunol (2013) 25(1):13-8. doi:10.1016/j.coi.2012.12.006
14. Sun L, Wu J, Du F, Chen X, Chen ZJ. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science (2013) 339(6121):786-91. doi:10.1126/science.1232458
15. Feng Z, Hensley L, McKnight KL, Hu F, Madden V, Ping L, et al. A pathogenic picornavirus acquires an envelope by hijacking cellular membranes. Nature (2013) 496(7445):367-71. doi:10.1038/nature12029
16. Kowalinski E, Lunardi T, McCarthy AA, Louber J, Brunel J, Grigorov B, et al. Structural basis for the activation of innate immune pattern-recognition receptor RIG-I by viral RNA. Cell (2011) 147(2):423-35. doi:10.1016/j.cell.2011.09.039
17. Jiang F, Ramanathan A, Miller MT, Tang GQ, Gale M, Patel SS, et al. Structural basis of RNA recognition and activation by innate immune receptor RIG-I. Nature (2011) 479(7373):423-7. doi:10.1038/nature10537
18. Luo D, Ding SC, Vela A, Kohlway A, Lindenbach BD, Pyle AM. Structural insights into RNA recognition by RIG-I. Cell (2011) 147(2):409-22. doi:10.1016/j.cell.2011.09.023
19. Zeng W, Sun L, Jiang X, Chen X, Hou F, Adhikari A, et al. Reconstitution of the RIG-I pathway reveals a signaling role of unanchored polyubiquitin chains in innate immunity. Cell (2010) 141(2):315-30. doi:10.1016/j.cell.2010.03.029
20. Berke IC, Modis Y. MDA5 cooperatively forms dimers and ATP-sensitive filaments upon binding double-stranded RNA. EMBO J (2012) 31(7):1714-26. doi:10.1038/emboj.2012.19
21. Peisley A, Lin C, Wu B, Orme-Johnson M, Liu M, Walz T, et al. Cooperative assembly and dynamic disassembly of MDA5 filaments for viral dsRNA recognition. Proc Natl Acad Sci U S A (2011) 108(52):21010-5. doi:10.1073/pnas.1113651108
22. Berke IC, Yu X, Modis Y, Egelman EH. MDA5 assembles into a polar helical filament on double-stranded RNA. Proc Natl Acad Sci U S A (2012) 109:18437-41. doi:10.1073/pnas.1212186109
23. Takahasi K, Kumeta H, Tsuduki N, Narita R, Shigemoto T, Hirai R, et al. 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 (2009) 284(26):17465-74. doi:10.1074/jbc.M109.007179
24. Li X, Lu C, Stewart M, Xu H, Strong RK, Igumenova T, et al. Structural basis of double-stranded RNA recognition by the RIG-I like receptor MDA5. Arch Biochem Biophys (2009) 488(1):23-33. doi:10.1016/j.abb.2009.06.008
25. 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. doi:10.1016/j.cell.2011.06.041
26. Jiang X, Kinch LN, Brautigam CA, Chen X, Du F, Grishin NV, et al. Ubiquitin-induced oligomerization of the RNA sensors RIG-I and MDA5 activates antiviral innate immune response. Immunity (2012) 36:959-73. doi:10.1016/j.immuni.2012.03.022
27. Arimoto K, Takahashi H, Hishiki T, Konishi H, Fujita T, Shimotohno K. Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125. Proc Natl Acad Sci U S A (2007) 104(18):7500-5. doi:10.1073/pnas.0611551104
28. Meylan E, Curran J, Hofmann K, Moradpour D, Binder M, Bartenschlager R, et al. Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature (2005) 437(7062):1167-72. doi:10.1038/nature04193
29. 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 U S A (2005) 102(49):17717-22. doi:10.1073/pnas.0508531102
30. Childs KS, Randall RE, Goodbourn S. LGP2 plays a critical role in sensitizing mda-5 to activation by double-stranded RNA. PLoS One (2013) 8(5):e64202. doi:10.1371/journal.pone.0064202
31. Deddouche S, Goubau D, Rehwinkel J, Chakravarty P, Begum S, Maillard PV, et al. Identification of an LGP2-associated MDA5 agonist in picornavirus-infected cells. Elife (2014) 3:e01535. doi:10.7554/eLife.01535
32. Rothenfusser S, Goutagny N, DiPerna G, Gong M, Monks BG, Schoenemeyer A, et al. The RNA helicase Lgp2 inhibits TLR-independent sensing of viral replication by retinoic acid-inducible gene-I. J Immunol (2005) 175(8):5260-8. doi:10.4049/jimmunol.175.8.5260
33. 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(5):2851-8. doi:10.4049/jimmunol.175.5.2851
34. Peisley A, Wu B, Yao H, Walz T, Hur S. RIG-I forms signaling-competent filaments in an ATP-dependent, ubiquitin-independent manner. Mol Cell (2013) 51(5):573-83. doi:10.1016/j.molcel.2013.07.024
35. Peisley A, Wu B, Xu H, Chen ZJ, Hur S. Structural basis for ubiquitin-mediated antiviral signal activation by RIG-I. Nature (2014) 509(7498):110-4. doi:10.1038/nature13140
36. Xu H, He X, Zheng H, Huang LJ, Hou F, Yu Z, et al. Structural basis for the prion-like MAVS filaments in antiviral innate immunity. Elife (2014) 3:e01489. doi:10.7554/eLife.01489
37. Wu B, Peisley A, Richards C, Yao H, Zeng X, Lin C, et al. Structural basis for dsRNA recognition, filament formation, and antiviral signal activation by MDA5. Cell (2013) 152(1-2):276-89. doi:10.1016/j.cell.2012.11.048
38. Peisley A, Jo MH, Lin C, Wu B, Orme-Johnson M, Walz T, et al. Kinetic mechanism for viral dsRNA length discrimination by MDA5 filaments. Proc Natl Acad Sci U S A (2012) 109(49):E3340-9. doi:10.1073/pnas.1208618109
39. Patel JR, Jain A, Chou YY, Baum A, Ha T, Garcia-Sastre A. ATPase-driven oligomerization of RIG-I on RNA allows optimal activation of type-I interferon. EMBO Rep (2013) 14(9):780-7. doi:10.1038/embor.2013.102
40. Murali A, Li X, Ranjith-Kumar CT, Bhardwaj K, Holzenburg A, Li P, et al. Structure and function of LGP2, a DEX(D/H) helicase that regulates the innate immunity response. J Biol Chem (2008) 283(23):15825-33. doi:10.1074/jbc.M800542200
41. Li X, Ranjith-Kumar CT, Brooks MT, Dharmaiah S, Herr AB, Kao C, et al. The RIG-I-like receptor LGP2 recognizes the termini of double-stranded RNA. J Biol Chem (2009) 284(20):13881-91. doi:10.1074/jbc.M900818200
42. Bruns AM, Pollpeter D, Hadizadeh N, Myong S, Marko JF, Horvath CM. ATP hydrolysis enhances RNA recognition and antiviral signal transduction by the innate immune sensor, laboratory of genetics and physiology 2 (LGP2). J Biol Chem (2013) 288(2):938-46. doi:10.1074/jbc.M112.424416
43. Gack MU, Shin YC, Joo CH, Urano T, Liang C, Sun L, et al. TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature (2007) 446(7138):916-20. doi:10.1038/nature05732
44. Binder M, Eberle F, Seitz S, Mucke N, Huber CM, Kiani N, et al. Molecular mechanism of signal perception and integration by the innate immune sensor retinoic acid-inducible gene-I (RIG-I). J Biol Chem (2011) 289(31):27278-87. doi:10.1074/jbc.M111.256974
45. Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, et al. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol (2004) 5(7):730-7. doi:10.1038/ni1087
46. Lin SC, Lo YC, Wu H. Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling. Nature (2010) 465(7300):885-90. doi:10.1038/nature09121
47. Cai X, Chen J, Xu H, Liu S, Jiang QX, Halfmann R, et al. Prion-like polymerization underlies signal transduction in antiviral immune defense and inflammasome activation. Cell (2014) 156(6):1207-22. doi:10.1016/j.cell.2014.01.063
48. Yu CY, Chiang RL, Chang TH, Liao CL, Lin YL. The interferon stimulator mitochondrial antiviral signaling protein facilitates cell death by disrupting the mitochondrial membrane potential and by activating caspases. J Virol (2010) 84(5):2421-31. doi:10.1128/JVI.02174-09
49. Dixit E, Boulant S, Zhang Y, Lee AS, Odendall C, Shum B, et al. Peroxisomes are signaling platforms for antiviral innate immunity. Cell (2010) 141(4):668-81. doi:10.1016/j.cell.2010.04.018
50. Okin D, Medzhitov R. Evolution of inflammatory diseases. Curr Biol (2012) 22(17):R733-40. doi:10.1016/j.cub.2012.07.029
51. Oshiumi H, Miyashita M, Matsumoto M, Seya T. A distinct role of Riplet-mediated K63-linked polyubiquitination of the RIG-I repressor domain in human antiviral innate immune responses. PLoS Pathog (2013) 9(8):e1003533. doi:10.1371/journal.ppat.1003533
52. Fan Y, Mao R, Yu Y, Liu S, Shi Z, Cheng J, et al. USP21 negatively regulates antiviral response by acting as a RIG-I deubiquitinase. J Exp Med (2014) 211(2):313-28. doi:10.1084/jem.20122844
53. Gack MU, Nistal-Villan E, Inn KS, Garcia-Sastre A, Jung JU. Phosphorylation-mediated negative regulation of RIG-I antiviral activity. J Virol (2010) 84(7):3220-9. doi:10.1128/JVI.02241-09
54. Nistal-Villan E, Gack MU, Martinez-Delgado G, Maharaj NP, Inn KS, Yang H, et al. Negative role of RIG-I serine 8 phosphorylation in the regulation of interferon-beta production. J Biol Chem (2010) 285(26):20252-61. doi:10.1074/jbc.M109.089912
55. Wies E, Wang MK, Maharaj NP, Chen K, Zhou S, Finberg RW, et al. Dephosphorylation of the RNA sensors RIG-I and MDA5 by the phosphatase PP1 is essential for innate immune signaling. Immunity (2013) 38(3):437-49. doi:10.1016/j.immuni.2012.11.018
56. Maharaj NP, Wies E, Stoll A, Gack MU. Conventional protein kinase C-alpha (PKC-alpha) and PKC-beta negatively regulate RIG-I antiviral signal transduction. J Virol (2012) 86(3):1358-71. doi:10.1128/JVI.06543-11
57. Zinzula L, Tramontano E. Strategies of highly pathogenic RNA viruses to block dsRNA detection by RIG-I-like receptors: hide, mask, hit. Antiviral Res (2013) 100(3):615-35. doi:10.1016/j.antiviral.2013.10.002
58. Wang B, Xi X, Lei X, Zhang X, Cui S, Wang J, et al. Enterovirus 71 protease 2Apro targets MAVS to inhibit anti-viral type I interferon responses. PLoS Pathog (2013) 9(3):e1003231. doi:10.1371/journal.ppat.1003231
59. Chen Z, Benureau Y, Rijnbrand R, Yi J, Wang T, Warter L, et al. GB virus B disrupts RIG-I signaling by NS3/4A-mediated cleavage of the adaptor protein MAVS. J Virol (2007) 81(2):964-76. doi:10.1128/JVI.02076-06
60. Mukherjee A, Morosky SA, Delorme-Axford E, Dybdahl-Sissoko N, Oberste MS, Wang T, et al. The coxsackievirus B 3C protease cleaves MAVS and TRIF to attenuate host type I interferon and apoptotic signaling. PLoS Pathog (2011) 7(3):e1001311. doi:10.1371/journal.ppat.1001311
61. Motz C, Schuhmann KM, Kirchhofer A, Moldt M, Witte G, Conzelmann KK, et al. Paramyxovirus V proteins disrupt the fold of the RNA sensor MDA5 to inhibit antiviral signaling. Science (2013) 339(6120):690-3. doi:10.1126/science.1230949
62. Ramachandran S, Kota P, Ding F, Dokholyan NV. Automated minimization of steric clashes in protein structures. Proteins (2011) 79(1):261-70. doi:10.1002/prot.22879
63. Ramanan P, Edwards MR, Shabman RS, Leung DW, Endlich-Frazier AC, Borek DM, et al. Structural basis for Marburg virus VP35-mediated immune evasion mechanisms. Proc Natl Acad Sci U S A (2012) 109(50):20661-6. doi:10.1073/pnas.1213559109
64. Leung DW, Prins KC, Borek DM, Farahbakhsh M, Tufariello JM, Ramanan P, et al. Structural basis for dsRNA recognition and interferon antagonism by Ebola VP35. Nat Struct Mol Biol (2010) 17(2):165-72. doi:10.1038/nsmb.1765
65. Hastie KM, Kimberlin CR, Zandonatti MA, MacRae IJ, Saphire EO. Structure of the Lassa virus nucleoprotein reveals a dsRNA-specific 3' to 5' exonuclease activity essential for immune suppression. Proc Natl Acad Sci U S A (2011) 108(6):2396-401. doi:10.1073/pnas.1016404108
66. Hastie KM, Liu T, Li S, King LB, Ngo N, Zandonatti MA, et al. Crystal structure of the Lassa virus nucleoprotein-RNA complex reveals a gating mechanism for RNA binding. Proc Natl Acad Sci U S A (2011) 108(48):19365-70. doi:10.1073/pnas.1108515108
67. Qi X, Lan S, Wang W, Schelde LM, Dong H, Wallat GD, et al. Cap binding and immune evasion revealed by Lassa nucleoprotein structure. Nature (2010) 468(7325):779-83. doi:10.1038/nature09605
68. Jiang X, Huang Q, Wang W, Dong H, Ly H, Liang Y, et al. Structures of arenaviral nucleoproteins with triphosphate dsRNA reveal a unique mechanism of immune suppression. J Biol Chem (2013) 288(23):16949-59. doi:10.1074/jbc.M112.420521
69. Brubaker SW, Gauthier AE, Mills EW, Ingolia NT, Kagan JC. A bicistronic MAVS transcript highlights a class of truncated variants in antiviral immunity. Cell (2014) 156(4):800-11. doi:10.1016/j.cell.2014.01.021