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Acta Microbiologica Sinica 48(10) 1418~1423; 4 October 2008 ISSN 0001-6209; CN11-1995/Q http://journals.im.ac.cn RIG-I RNA * ( 100071) RIG-I RIG-I like receptors RLR RNA RLR RLR RLR RNA RNA RIG-I MDA5 RLR R37 A 0001-6209 (2008) 10-1418-06 pattern recognition receptors PRR pathogen-associated molecular patterns PAMP IFN Toll Toll-like receptor TLR PRR RNA TLR3 dsrna TLR7 TLR8 ssrna TLR RNA RNA TLR RIG-I RIG-I-like receptor RLR PRR RNA 1 RLR RLR 3 -I retinoic acid induced gene I RIG-I 5 melanoma differentiation associated gene 5 MDA5 LGP2 laboratory of genetics and physiology 2 RIG-I [1] APL 2004 Yoneyama RIG-I RNA I [2] RIG-I cdna 3.0 kb 925 RIG-I N 2 caspase activation and recruitment domain CARD DExD/H C repressor domain RD CARD CARD IFN ATP TAS ATP K270 K270A RIG-I [3] C RD RNA RIG-I RIG-I N CARD C RD RNA RIG-I ATP CARD [4] : (30570084, 30600530); 973 (2002CB513205) * Tel: +86-10-66948604; Fax: +86-10-63898239; E-mail: qinede@sohu.com : (1979 ),,,, E-mail: cfqin@hotmail.com : 2008-03-19; : 2008-05-18

RIG-I RNA./ (2008) 48(10) 1419 MDA5 RIG-I CARD 23 35 LGP2 CARD RIG-I MDA5 31 41 C RIG-I RD RLR RNA RIG-I dsrna poly I:C poly A:U HCV [2] MDA5 poly I:C MDA5 poly I C [5,6] 5 - ssrna 3p-RNA RIG-I [7-8] 3p-RNA RIG-I RNA RNA RNA mrna 5 - trna 5 - rrna rrnp RIG-I RNA 5 - Vpg [9] RNA RIG-I RLR cdcs RNA pdcs TLR7/8 TLR9 RNA [10] RLR MDA5 RNA RIG-I RNA RLR RNA RNA EB EB DNA RNA RIG-I [11] DNA RLR 2 RLR RLR 2005 4 RLR IPS-1 MAVS VISA Cardif [12 15] IPS-1 IFN-α/β NF-κB IPS-1 RIG-1/MDA5 RNA [16] IPS-1 540 63 kda CARD CARD RIG-I/MDA5 CARD 2.1Ǻ [17] CARD TRAF3 TRAF6 TRAF2 RIP1 FADD IPS-1 RLR TLR IPS-1 IPS-1 IPS-1 IPS-1 TRAF3 TRAF [18] IPS-1 TRAF3 TBK-1 IKKi TBK-1/IKKε TANK IPS-1 TRAF3 [18] TANK NAP1 SINTBAD TBK-1/IKKi RLR IKKi STAT1 interferon-stimulated gene ISG [19] TBK-1/IKKi IRF-3 IRF-7 IRF-3/IRF-7 IFN-α/β IFN-α/β JAK-STAT ISGs IPS-1 TRAF6/ TRAF2 IKKα/β/γ NF-κB NAP1 FADD FADD IPS-1 caspase-8/-10 NF-κB [20] 3 RLR RLR ISGs IFN-α/β JAK-SATA RLR RLR IRF-1 IFN-γ LPS TNF-α RIG-I MDA5 IRF-3 IRF-3

1420 Chengfeng Qin et al. /Acta Microbiologica Sinica (2008) 48(10) MDA5 IRF-3 MDA5 [21] LGP2 RLR LGP2 RNA CARD IPS-1 RIG-I LGP2 C RD RIG-I RD RIG-I [3] Venkataraman [22] LGP2 (VSV) EMCV LGP2 LGP2 RIG-I MDA5 LGP2 poly I:C LGP2 RIG-I/MDA5 RLR TRIM RING B / B box/ccd SPRY TRIM25 SPRY RIG-I CARD Lys63 IPS-1 RIG-I TRIM25 [23] TRIM25 RLR E3 RNF125 RIG-I MDA5 IPS-1 IFN RNF125 RNF125 RLR [24] TRAF3 E3 IPS-1 RLR DUBA TRAF3 RLR [25] NF-κB A20 2 N C N A20 TRIF RIG-I NF-κB IRF-3 IRF-7 RIG-I [26] Atg5-Atg12 Atg5 Atg12 Atg5 Atg12 VSV [27] Atg5-Atg12 RIG-I IPS-1 CARD dihydroxyacetone kinase DAK MDA5 CARD MDA5 [28] DAK RIG-I SOCS1 SOCS3 RIG-I [29] 4 RLR RNA RIG-I MDA5 IFN-α/β RNA RLR 1 1 RLR Fig. 1 Evasion of RLR signaling by RNA viruses. EV: ebola virus; IAV: influenza A virus; SeV: sendai virus; HAV: hepatitis A virus; HCV: hepatitis C virus; GBV: GB virus.

RIG-I RNA./ (2008) 48(10) 1421 HCV NS3/4a TLR3 TRIF NS5A ISGs HCV RIG-I HCV NS3/4A IPS-1 RIG-I [30-31] NS3 70 kda N NS4a NS3/4a NS3 DExD/H NS4A NS4a NS3/4A IPS-1 C508 NS3/4A RIG-1 IFN-α/β HCV NS3/4A IPS-1 RIG-I [32] NS3/4A IPS-1 Loo [33] IPS-1 IPS-1 RIG-I V MDA5 RIG-I [34] NS1 dsrna RIG-I RIG-I [35] GB RLR RLR JAK-STAT JAK-STAT RLR 5 RLR PRR RNA RLR 3p-RNA RIG-I RNase L RNA 3 - RNA RIG-I [36] RLR Kato RIG-I [5] RIG-I MDA-5 RLR RIG-I [10] [37] Su RIG-I RIG-I [38] Caenorhabditis elegans RLR DExD/H RNA [39] sirna shrna RNA RLR RLR NS3/4a PRR Coley TLR [40] MDA5 poly I C RLR RLR [1] Liu TX, Zhang JW, Tao J, et al. Gene expression networks underlying retinoic acid-induced differentiation of acute promyelocytic leukemia cells. Blood, 2000, 96(4): 1496 1504. [2] Yoneyama M, Kikuchi M, Natsukawa T, et al. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol, 2004, 59(7): 730 737. [3] Saito T, Hirai R, Loo YM, et al. Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2. Proc Natl Acad Sci USA, 2007, 104(2): 582 587.

1422 Chengfeng Qin et al. /Acta Microbiologica Sinica (2008) 48(10) [4] Cui S, Eisenächer K, Kirchhofer A, et al. The C-terminal regulatory domain is the RNA 5 -triphosphate sensor of RIG-I. Mol Cell, 2008, 29(2): 169 179. [5] Kato H, Takeuchi O, Sato S, et al. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature, 2006, 441(7089): 101 105. [6] Gitlin L, Barchet W, Gilfillan S, et al. Essential role of mda-5 in type I IFN responses to polyriboinosinic: polyribocytidylic acid and encephalomyocarditis picornavirus. Proc Natl Acad Sci USA, 2006, 103(22): 8459 8464. [7] Hornung V, Ellegast J, Kim S, et al. 5 -Triphosphate RNA is the ligand for RIG-I. Science, 2006, 314(5801): 994 997. [8] Pichlmair A, Schulz O, Tan C, et al. RIG-I-mediated antiviral responses to single-stranded RNA bearing 5 -phosphates. Science, 2006, 314(5801): 997 1001. [9] Pathak HB, Arnold JJ, Wiegand PN, et al. 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