TLR signaling

Cell Death and Differentiation

Volumn 13, Issue 5, 2006, Pages 816-825

  Kawai, T ^a   Akira, S ^a,b  

^a JAPAN SCIENCE AND TECHNOLOGY AGENCY   (Japan)

^b OSAKA UNIVERSITY   (Japan)

Author keywords

Inflammatory cytokines; Innate immunity; Signal transduction; Toll like receptors; Type I interferon

Indexed keywords

ADAPTOR PROTEIN; ALPHA INTERFERON; BACTERIAL PROTEIN; BACTERIUM LIPOPOLYSACCHARIDE; BETA INTERFERON; FLAGELLIN; I KAPPA B KINASE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERFERON REGULATORY FACTOR; INTERLEUKIN 12; INTERLEUKIN 1BETA; INTERLEUKIN 6; LIPOPEPTIDE; LIPOPROTEIN; MYELOID DIFFERENTIATION FACTOR 88; PEPTIDOGLYCAN; TOLL LIKE RECEPTOR; TOLL LIKE RECEPTOR 3; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 8; TOLL LIKE RECEPTOR 9; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR AP 1; TUMOR NECROSIS FACTOR ALPHA; VIRUS PROTEIN;

ANTIGEN PRESENTING CELL; ANTIINFLAMMATORY ACTIVITY; ANTIVIRAL ACTIVITY; CELL MATURATION; CYTOKINE PRODUCTION; DENDRITIC CELL; ERADICATION THERAPY; GRAM NEGATIVE BACTERIUM; GRAM POSITIVE BACTERIUM; HUMAN; IMMUNE RESPONSE; INNATE IMMUNITY; MICROBIAL IMMUNITY; MOLECULAR RECOGNITION; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN FAMILY; PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ADAPTOR PROTEINS, VESICULAR TRANSPORT; ANIMALS; DEAD-BOX RNA HELICASES; DROSOPHILA; GENE EXPRESSION REGULATION; HUMANS; IMMUNITY, NATURAL; INTERFERON REGULATORY FACTORS; MEMBRANE PROTEINS; MICE; MODELS, BIOLOGICAL; MYELOID DIFFERENTIATION FACTOR 88; NERVE TISSUE PROTEINS; NF-KAPPA B; RNA HELICASES; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTORS; TRANSCRIPTION FACTOR AP-1;

ALPHAVIRUS; BACTERIA (MICROORGANISMS); NEGIBACTERIA; POSIBACTERIA;

EID: 33645960706     PISSN: 13509047     EISSN: 14765403     Source Type: Journal    
DOI: 10.1038/sj.cdd.4401850     Document Type: Review

References (89)

1. Akira S, Takeda K and Kaisho T (2001) Toll-like receptors: Critical proteins linking innate and acquired immunity. Nat. Immunol. 2: 675-680
2. Lemaitre B, Nicolas E, Michaut L, Reichhart JM and Hoffmann JA (1996) The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86: 973-983
3. Hoffmann JA (2003) The immune response of Drosophila. Nature 426: 33-38
4. Medzhitov R, Preston-Hurlburt P and Janeway CJ (1997) A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388: 394-397
5. Poltorak A, He X, Smirnova I, Liu MY, Van Huffel C, Du X, Birdwell D, Alejos E, Silva M, Galanos C, Freudenberg M, Ricciardi-Castagnoli P, Layton B and Beutler B (1998) Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: Mutations in Tlr4 gene. Science 282: 2085-2088
6. Hoshino K, Takeuchi O, Kawai T, Sanjo H, Ogawa T, Takeda Y, Takeda K and Akira S (1999) Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: Evidence for TLR4 as the Lps gene product. J. Immunol. 162: 3749-3752
7. Takeda K and Akira S (2005) Toll-like receptors in innate immunity. Int. Immunol. 17: 1-14
8. Takeuchi O, Hoshino K, Kawai T, Sanjo H, Takada H, Ogawa T, Takeda K and Akira S (1999) Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components. Immunity 11: 443-451
9. Takeuchi O, Kaufmann A, Grote K, Kawai T, Hoshino K, Morr M, Muhlradt PF and Akira S (2000) Preferentially the R-stereoisomer of the mycoplasmal lipopeptide macrophage-activating lipopeptide-2 activates immune cells through a toll-like receptor 2- and MyD88-dependent signaling pathway. J. Immunol. 164: 554-557
10. Takeuchi O, Sato S, Horiuchi T, Hoshino K, Takeda K, Dong Z, Modlin RL and Akira S (2002) Role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins. J. Immunol. 169: 10-14
11. Takeuchi O, Kawai T, Muhlradt PF, Morr M, Radolf JD, Zychlinsky A, Takeda K and Akira S (2001) Discrimination of bacterial lipoproteins by Toll-like receptor 6. Int. Immunol. 13: 933-940
12. Ozinsky A, Underhill DM, Fontenot JD, Hajjar AM, Smith KD, Wilson CB, Schroeder L and Aderem A (2000) The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors. Proc. Natl. Acad. Sci. USA 97: 13766-13771
13. Alexopoulou L, Holt AC, Medzhitov R and Flavell RA (2001) Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413: 732-738
14. Hayashi F, Smith KD, Ozinsky A, Hawn TR, Yi EC, Goodlett DR, Eng JK, Akira S, Underhill DM and Aderem A (2001) The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410: 1099-1103
15. Zhang D, Zhang G, Hayden MS, Greenblatt MB, Bussey C, Flavell RA and Ghosh S (2004) A toll-like receptor that prevents infection by uropathogenic bacteria. Science 303: 1522-1526
16. Yarovinsky F, Zhang D, Andersen JF, Bannenberg GL, Serhan CN, Hayden MS, Hieny S, Sutterwala FS, Flavell RA, Ghosh S and Sher A (2005) TLR11 activation of dendritic cells by a protozoan profilin-like protein. Science 308: 1626-1629
17. Hemmi H, Kaisho T, Takeuchi O, Sato S, Sanjo H, Hoshino K, Horiuchi T, Tomizawa H, Takeda K and Akira S (2002) Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat. Immunol. 3: 196-200
18. Diebold SS, Kaisho T, Hemmi H, Akira S and Reis e Sousa C (2004) Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 303: 1529-1531
19. Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S, Lipford G, Wagner H and Bauer S (2004) Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 303: 1526-1529
20. Heil F, Ahmad-Nejad P, Hemmi H, Hochrein H, Ampenberger F, Gellert T, Dietrich H, Lipford G, Takeda K, Akira S, Wagner H and Bauer S (2003) The Toll-like receptor 7 (TLR7)-specific stimulus loxoribine uncovers a strong relationship within the TLR7 8 and 9 subfamily. Eur. J. Immunol. 33: 2987-2997
21. Jurk M, Heil F, Vollmer J, Schetter C, Krieg AM, Wagner H, Lipford G and Bauer S (2002) Human TLR7 or TLR8 independently confer responsiveness to the antiviral compound R-848. Nat. Immunol. 3: 499
22. Lund JM, Alexopoulou L, Sato A, Karow M, Adams NC, Gale NW, Iwasaki A and Flavell RA (2004) Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proc. Natl. Acad. Sci. USA 101: 5598-5603
23. Hornung V, Guenthner-Biller M, Bourquin C, Ablasser A, Schlee M, Uematsu S, Noronha A, Manoharan M, Akira S, de Fougerolles A, Endres S and Hartmann G (2005) Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7. Nat. Med. 11: 263-270
24. Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H, Matsumoto M, Hoshino K, Wagner H, Takeda K and Akira S (2000) A Toll-like receptor recognizes bacterial DNA. Nature 408: 740-745
25. Krug A, French AR, Barchet W, Fischer JA, Dzionek A, Pingel JT, Orihuela MM, Akira S, Yokoyama WM and Colonna M (2004) TLR9-dependent recognition of MCMV by IPC and DC generates coordinated cytokine responses that activate antiviral NK cell function. Immunity 21: 107-119
26. Lund J, Sato A, Akira S, Medzhitov R and Iwasaki A (2003) Toll-like receptor 9-mediated recognition of Herpes simplex virus-2 by plasmacytoid dendritic cells. J. Exp. Med. 198: 513-520
27. Coban C, Ishii KJ, Kawai T, Hemmi H, Sato S, Uematsu S, Yamamoto M, Takeuchi O, Itagaki S, Kumar N, Horii T and Akira S (2005) Toll-like receptor 9 mediates innate immune activation by the malaria pigment hemozoin. J. Exp. Med. 201: 19-25
28. Iwasaki A and Medzhitov R (2004) Toll-like receptor control of the adaptive immune responses. Nat. Immunol. 5: 987-995
29. Akira S and Takeda K (2004) Toll-like receptor signalling. Nat. Rev. Immunol. 4: 499-511
30. Karin M and Greten FR (2005) NF-kappaB: Linking inflammation and immunity to cancer development and progression. Nat. Rev. Immunol. 5: 749-759
31. Shaulian E and Karin M (2002) AP-1 as a regulator of cell life and death. Nat. Cell. Biol. 4: 131-136
32. Kobayashi K, Hernandez LD, Galan JE, Janeway Jr. CA, Medzhitov R and Flavell RA (2002) IRAK-M is a negative regulator of Toll-like receptor signaling. Cell 110: 191-202
33. Suzuki N, Suzuki S, Duncan GS, Millar DG, Wada T, Mirtsos C, Takada H, Wakeham A, Itie A, Li S, Penninger JM, Wesche H, Ohashi PS, Mak TW and Yeh WC (2002) Severe impairment of interleukin-1 and Toll-like receptor signalling in mice lacking IRAK-4. Nature 416: 750-756
34. Picard C, Puel A, Bonnet M, Ku CL, Bustamante J, Yang K, Soudais C, Dupuis S, Feinberg J, Fieschi C, Elbim C, Hitchcock R, Lammas D, Davies G, Al-Ghonaium A, Al-Rayes H, Al-Jumaah S, Al-Hajjar S, Al-Mohsen IZ, Frayha HH, Rucker R, Hawn TR, Aderem A, Tufenkeji H, Haraguchi S, Day NK, Good RA, Gougerot-Pocidalo MA, Ozinsky A and Casanova JL (2003) Pyogenic bacterial infections in humans with IRAK-4 deficiency. Science 299: 2076-2079
35. Chen ZJ (2005) Ubiquitin signalling in the NF-kappaB pathway. Nat. Cell Biol. 7: 758-765
36. Sun L and Chen ZJ (2004) The novel functions of ubiquitination in signaling. Curr. Opin. Cell Biol. 16: 119-126
37. Sato S, Sanjo H, Takeda K, Ninomiya-Tsuji J, Yamamoto M, Kawai T, Matsumoto K, Takeuchi O and Akira S (2005) Essential function for the kinase TAK1 in innate and adaptive immune responses. Nat. Immunol. 6: 1087-1095
38. Huang Q, Yang J, Lin Y, Walker C, Cheng J, Liu ZG and Su B (2004) Differential regulation of interleukin 1 receptor and Toll-like receptor signaling by MEKK3. Nat. Immunol. 5: 98-103
39. Dumitru CD, Ceci JD, Tsatsanis C, Kontoyiannis D, Stamatakis K, Lin JH, Patriotis C, Jenkins NA, Copeland NG, Kollias G and Tsichlis PN (2000) TNF-alpha induction by LPS is regulated posttranscriptionally via a Tpl2/ ERK-dependent pathway. Cell 103: 1071-1083
40. Sugimoto K, Ohata M, Miyoshi J, Ishizaki H, Tsuboi N, Masuda A, Yoshikai Y, Takamoto M, Sugane K, Matsuo S, Shimada Y and Matsuguchi T (2004) A serine/threonine kinase Cot/Tpl2 modulates bacterial DNA-induced IL-12 production and Th cell differentiation. J. Clin. Invest. 114: 857-866
41. Yamamoto M, Sato S, Hemmi H, Sanjo H, Uematsu S, Kaisho T, Hoshino K, Takeuchi O, Kobayashi M, Fujita T, Takeda K and Akira S (2002) Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4. Nature 420: 324-329
42. Horng T, Barton GM, Flavell RA and Medzhitov R (2002) The adaptor molecule TIRAP provides signalling specificity for Toll-like receptors. Nature 420: 329-333
43. Kawai T, Takeuchi O, Fujita T, Inoue J, Muhlradt PF, Sato S, Hoshino K and Akira S (2001) Lipopolysaccharide stimulates the MyD88-independent pathway and results in activation of IFN-regulatory factor 3 and the expression of a subset of lipopolysaccharide-inducible genes. J. Immunol. 167: 5887-5894
44. Hacker H, Vabulas R.M, Takeuchi O, Hoshino K, Akira S and Wagner H (2000) Immune cell activation by bacterial CpG-DNA through myeloid differentiation marker 88 and tumor necrosis factor receptor-associated factor (TRAF)6. J. Exp. Med. 192: 595-600
45. Schnare M, Holt A.C, Takeda K, Akira S and Medzhitov R (2000) Recognition of CpG DNA is mediated by signaling pathways dependent on the adaptor protein MyD88. Curr. Biol. 10: 1139-1142
46. Kawai T, Adachi O, Ogawa T, Takeda K and Akira S (1999) Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity 11: 115-122
47. Theofilopoulos AN, Baccala R, Beutler B and Kono DH (2005) Type I interferons (alpha/beta) in immunity and autoimmunity. Annu. Rev. Immunol. 23: 307-336
48. Yamamoto M, Sato S, Mori K, Hoshino K, Takeuchi O, Takeda K and Akira S (2002) A novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling. J. Immunol. 169: 6668-6672
49. Oshiumi H, Matsumoto M, Funami K, Akazawa T and Seya T (2003) TICAM-1 an adaptor molecule that participates in Toll-like receptor 3-mediated interferon-beta induction. Nat. Immunol. 4: 161-167
50. Yamamoto M, Sato S, Hemmi H, Hoshino K, Kaisho T, Sanjo H, Takeuchi O, Sugiyama M, Okabe M, Takeda K and Akira S (2003) Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science 301: 640-643
51. Hoebe K, Du X, Georgel P, Janssen E, Tabeta K, Kim SO, Goode J, Lin P, Mann N, Mudd S, Crozat K, Sovath S, Han J and Beutler B (2003) Identification of Lps2 as a key transducer of MyD88-independent TIR signalling. Nature 424: 743-748
52. Yamamoto M, Sato S, Hemmi H, Uematsu S, Hoshino K, Kaisho T, Takeuchi O, Takeda K and Akira S (2003) TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway. Nat. Immunol. 4: 1144-1150
53. Meylan E, Burns K, Hofmann K, Blancheteau V, Martinon F, Kelliher M and Tschopp J (2004) RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappaB activation. Nat. Immunol. 5: 503-507
54. Cusson-Hermance N, Lee TH, Fitzgerald KA and Kelliher MA (2005) Rip1 mediates the Trif-dependent toll-like receptor 3 and 4-induced NF-kappa B activation but does not contribute to IRF-3 activation. J. Biol. Chem. 280: 36560-36566
55. Sato S, Sugiyama M, Yamamoto M, Watanabe Y, Kawai T, Takeda K and Akira S (2003) Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1 and activates two distinct transcription factors NF-kappa B and IFN-regulatory factor-3 in the Toll-like receptor signaling. J. Immunol. 171: 4304-4310
56. Gohda J, Matsumura T and Inoue J (2004) TNFR-associated factor (TRAF) 6 is essential for MyD88-dependent pathway but not toll/IL-1 receptor domain-containing adaptor-inducing IFN-beta (TRIF)-dependent pathway in TLR signaling. J. Immunol. 173: 2913-2917
57. Sharma S, tenOever BR, Grandvaux N, Zhou GP, Lin R and Hiscott J (2003) Triggering the interferon antiviral response through an IKK-related pathway. Science 300: 1148-1151
58. Fitzgerald KA, McWhirter SM, Faia KL, Rowe DC, Latz E, Golenbock DT, Coyle AJ, Liao SM and Maniatis T (2003) IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat. Immunol. 4: 491-496
59. McWhirter SM, Fitzgerald KA, Rosains J, Rowe DC, Golenbock DT and Maniatis T (2004) IFN-regulatory factor 3-dependent gene expression is defective in Tbk1-deficient mouse embryonic fibroblasts. Proc. Natl. Acad. Sci. USA 101: 233-238
60. Hemmi H, Takeuchi O, Sato S, Yamamoto M, Kaisho T, Sanjo H, Kawai T, Hoshino K, Takeda K and Akira S (2004) The roles of two (kappaB kinase-related kinases in lipopolysaccharide and double stranded RNA signaling and viral infection. J. Exp. Med. 199: 1641-1650
61. Perry AK, Chow EK, Goodnough JB, Yeh WC and Cheng G (2004) Differential requirement for TANK-binding kinase-1 in type I interferon responses to Toll-like receptor activation and viral infection. J. Exp. Med. 199: 1651-1658
62. Colonna M, Trinchieri G and Liu YJ (2004) Plasmacytoid dendritic cells in immunity. Nat. Immunol. 5: 1219-1226
63. Liu YJ (2005) IPC: Professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. Annu. Rev. Immunol. 23: 275-306
64. Honda K, Yanai H, Negishi H, Asagiri M, Sato M, Mizutani T, Shimada N, Ohba Y, Takaoka A, Yoshida N and Taniguchi T (2005) IRF-7 is the master regulator of type-I interferon-dependent immune responses. Nature 434: 772-777
65. Kawai T, Sato S, Ishii K.J, Coban C, Hemmi H, Yamamoto M, Terai K, Matsuda M, Inoue J, Uematsu S, Takeuchi O and Akira S (2004) Interferon-alpha induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6. Nat. Immunol. 5: 1061-1068
66. Honda K, Yanai H, Mizutani T, Negishi H, Shimada N, Suzuki N, Ohba Y, Takaoka A, Yeh WC and Taniguchi T (2004) Role of a transductional-transcriptional processor complex involving MyD88 and IRF-7 in Toll-like receptor signaling. Proc. Natl. Acad. Sci. USA 101: 15416-15421
67. Hemmi H, Kaisho T, Takeda K and Akira S (2003) The roles of Toll-like receptor 9 MyD88 and DNA-dependent protein kinase catalytic subunit in the effects of two distinct CpG DNAs on dendritic cell subsets. J. Immunol. 170: 3059-3064
68. Coccia EM, Severa M, Giacomini E, Monneron D, Remoli ME, Julkunen I, Cella M, Lande R and Uze G (2004) Viral infection and Toll-like receptor agonists induce a differential expression of type I and lambda interferons in human plasmacytoid and monocyte-derived dendritic cells. Eur. J. Immunol. 34: 796-805
69. Dai J, Megjugorac NJ, Amrute SB and Fitzgerald-Bocarsly P (2004) Regulation of IFN regulatory factor-7 and IFN-alpha production by enveloped virus and lipopolysaccharide in human plasmacytoid dendritic cells. J. Immunol. 173: 1535-1548
70. Uematsu S, Sato S, Yamamoto M, Hirotani T, Kato H, Takeshita F, Matsuda M, Coban C, Ishii KJ, Kawai T, Takeuchi O and Akira S (2005) Interleukin-1 receptor-associated kinase-1 (IRAK-1) plays an essential role for TLR7- and TLR9-mediated interferon-α induction. J. Exp. Med. 201: 915-923
71. Takaoka A, Yanai H, Kondo S, Duncan G, Negishi H, Mizutani T, Kano SI, Honda K, Ohba Y, Mak TW and Taniguchi T (2005) Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors. Nature 434: 243-249
72. Lin R, Yang L, Arguello M, Penafuerte C and Hiscott J (2005) A CRM1-dependent nuclear export pathway is involved in the regulation of IRF-5 subcellular localization. J. Biol. Chem. 280: 3088-3095
73. Schoenemeyer A, Barnes BJ, Mancl ME, Latz E, Goutagny N, Pitha PM, Fitzgerald KA and Golenbock DT (2005) The interferon regulatory factor IRF5 is a central mediator of TLR7 signaling. J. Biol. Chem. 280: 17005-17012
74. Tsujimura H, Tamura T, Kong HJ, Nishiyama A, Ishii KJ, Klinman DM and Ozato K (2004) Toll-like receptor 9 signaling activates NF-kappaB through IFN regulatory factor-8/IFN consensus sequence binding protein in dendritic cells. J. Immunol. 172: 6820-6827
75. Hornung V, Schlender J, Guenthner-Biller M, Rothenfusser S, Endres S, Conzelmann KK and Hartmann G (2004) Replication-dependent potent IFN-alpha induction in human plasmacytoid dendritic cells by a single-stranded RNA virus. J. Immunol. 173: 5935-5943
76. Krug A, Luker GD, Barchet W, Leib DA, Akira S and Colonna M (2004) Herpes simplex virus type 1 activates murine natural interferon-producing cells through toll-like receptor 9. Blood 103: 1433-1437
77. Edelmann KH, Richardson-Burns S, Alexopoulou L, Tyler KL, Flavell RA and Oldstone MB (2004) Does Toll-like receptor 3 play a biological role in virus infections? Virology 322: 231-238
78. Lopez CB, Moltedo B, Alexopoulou L, Bonifaz L, Flavell RA and Moran TM (2004) TLR-independent induction of dendritic cell maturation and adaptive immunity by negative-strand RNA viruses. J. Immunol. 173: 6882-6889
79. Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M, Taira K, Akira S and Fujita T (2004) The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat. Immunol. 5: 730-737
80. Kato H, Sato S, Yoneyama M, Yamamoto M, Uematsu S, Matsui K, Tsujimura T, Takeda K, Fujita T, Takeuchi O and Akira S (2005) Cell type specific involvement of RIG-I in antiviral response. Immunity 23: 19-28
81. Kang DC, Gopalkrishnan RV, Wu Q, Jankowsky E, Pyle AM and Fisher PB (2002) mda-5: An interferon-inducible putative RNA helicase with double-stranded RNA-dependent ATPase activity and melanoma growth-suppressive properties. Proc. Natl. Acad. Sci. USA 99: 637-642
82. Kovacsovics M, Martinon F, Micheau O, Bodmer JL, Hofmann K and Tschopp J (2002) Overexpression of Helicard a CARD-containing helicase cleaved during apoptosis accelerates DNA degradation. Curr. Biol. 12: 838-843
83. Andrejeva J, Childs KS, Young DF, Carlos TS, Stock N, Goodbourn S and 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. USA 101: 17264-17269
84. Yoneyama M, Kikuchi M, Matsumoto K, Imaizumi T, Miyagishi M, Taira K, Foy E, Loo YM, Gale MJ, Akira S, Yonehara S, Kato A and Fujita T (2005) Shared and unique functions of the DExD/H-Box helicases RIG-I MDA5 and LGP2 in antiviral innate immunity. J. Immunol. 175: 2851-2858
85. Kawai T, Takahashi K, Sato S, Coban C, Kumar H, Kato H, Ishii KJ, Takeuchi O and Akira S (2005) IPS-1; an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nat. Immunol. 6: 981-988
86. Seth RB, Sun L, Ea CK and Chen ZJ (2005) Identification and characterization of MAVS a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF3. Cell 122: 669-682
87. Xu LG, Wang YY, Han KJ, Li LY, Zhai Z and Shu HB (2005) VISA Is an adapter protein required for virus-triggered IFN-beta signaling. Mol. Cell 19: 727-740
88. Meylan E, Curran J, Hofmann K, Moradpour D, Binder M, Bartenschlager R and 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
89. Balachandran S, Thomas E and Barber GN (2004) A FADD-dependent innate immune mechanism in mammalian cells. Nature 432: 401-405