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PMID: 18703349 Published · ppublish English Journal Article Review

Negative regulation of cytoplasmic RNA-mediated antiviral signaling.

Cytokine ·Vol. 43 ·No. 3 ·2008-09-00 ·Pages 350-8

Komuro A, Bamming D, Horvath CM

Abstract

The recent, rapid progress in our understanding of cytoplasmic RNA-mediated antiviral innate immune signaling was initiated by the discovery of retinoic acid-inducible gene I (RIG-I) as a sensor of viral RNA. It is now widely recognized that RIG-I and related RNA helicases, melanoma differentiation-associated gene-5 (MDA5) and laboratory of genetics and physiology-2 (LGP2), can initiate and/or regulate RNA and virus-mediated type I IFN production and antiviral responses. As with other cytokine systems, production of type I IFN is a transient process, and can be hazardous to the host if unregulated, resulting in chronic cellular toxicity or inflammatory and autoimmune diseases. In addition, the RIG-I-like receptor (RLR) system is a fundamental target for virus-encoded immune suppression, with many indirect and direct examples of interference described. In this article, we review the current understanding of endogenous negative regulation in RLR signaling and explore direct inhibition of RLR signaling by viruses as a host immune evasion strategy.

MeSH Terms
Animals Autophagy-Related Protein 12 Autophagy-Related Protein 5 Cytokines/physiology DEAD Box Protein 58 DEAD-box RNA Helicases/physiology DNA-Binding Proteins Deubiquitinating Enzyme CYLD Endopeptidases/physiology Humans Immunity, Innate/physiology Interferon Type I/biosynthesis Interferon-Induced Helicase, IFIH1 Intracellular Signaling Peptides and Proteins/physiology Microtubule-Associated Proteins Mitochondrial Proteins/physiology NIMA-Interacting Peptidylprolyl Isomerase Nuclear Proteins/physiology Nuclear Receptor Co-Repressor 1 Peptidylprolyl Isomerase/physiology Phosphotransferases (Alcohol Group Acceptor)/physiology RNA Helicases/physiology RNA, Viral/analysis Repressor Proteins/physiology Signal Transduction/drug effects,physiology Small Ubiquitin-Related Modifier Proteins/physiology Tumor Necrosis Factor alpha-Induced Protein 3 Tumor Suppressor Proteins/physiology Ubiquitins/physiology
Chemicals
ATG12 protein, human ATG5 protein, human Autophagy-Related Protein 12 Autophagy-Related Protein 5 Cytokines DNA-Binding Proteins Interferon Type I Intracellular Signaling Peptides and Proteins Microtubule-Associated Proteins Mitochondrial Proteins NCOR1 protein, human NIMA-Interacting Peptidylprolyl Isomerase NLRX1 protein, human Ncor1 protein, mouse Nuclear Proteins Nuclear Receptor Co-Repressor 1 RNA, Viral Repressor Proteins SIKE protein, mouse Small Ubiquitin-Related Modifier Proteins Tumor Suppressor Proteins Ubiquitins ISG15 protein, human Phosphotransferases (Alcohol Group Acceptor) glycerone kinase DHX58 protein, human Endopeptidases OTUD5 protein, human CYLD protein, human Deubiquitinating Enzyme CYLD TNFAIP3 protein, human Tumor Necrosis Factor alpha-Induced Protein 3 Ddx58 protein, mouse Ifih1 protein, mouse DEAD Box Protein 58 DEAD-box RNA Helicases Interferon-Induced Helicase, IFIH1 RNA Helicases PIN1 protein, human Peptidylprolyl Isomerase Pin1 protein, mouse
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Komuro Akihiko
Department of Medicine, Northwestern University, Evanston, IL 60208, USA.
Bamming Darja
Horvath Curt M
References (141)
141 references, click to expand
  1. RNA- and virus-independent inhibition of antiviral signaling by RNA helicase LGP2.
    J Virol. 2006 Dec;80(24):12332-42 PMID: 17020950
  2. Activation of interferon regulatory factor 3 is inhibited by the influenza A virus NS1 protein.
    J Virol. 2000 Sep;74(17):7989-96 PMID: 10933707
  3. From ATP as substrate to ADP as coenzyme: functional evolution of the nucleotide binding subunit of dihydroxyacetone kinases.
    J Biol Chem. 2005 May 6;280(18):18321-5 PMID: 15753087
  4. The interplay between viruses and innate immune signaling: recent insights and therapeutic opportunities.
    Biochem Pharmacol. 2008 Feb 1;75(3):589-602 PMID: 17868652
  5. Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3'end formation of cellular pre-mRNAs.
    Mol Cell. 1998 Jun;1(7):991-1000 PMID: 9651582
  6. Double-stranded RNA binding by human cytomegalovirus pTRS1.
    J Virol. 2005 Jun;79(12):7311-8 PMID: 15919885
  7. Subversion of cellular autophagosomal machinery by RNA viruses.
    PLoS Biol. 2005 May;3(5):e156 PMID: 15884975
  8. The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4.
    Nature. 2004 Mar 18;428(6980):341-5 PMID: 15029200
  9. The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses.
    Nat Immunol. 2004 Oct;5(10):1052-60 PMID: 15334086
  10. Reversal of the interferon-sensitive phenotype of a vaccinia virus lacking E3L by expression of the reovirus S4 gene.
    J Virol. 1995 Jan;69(1):499-505 PMID: 7527085
  11. Activation of the beta interferon promoter by unnatural Sendai virus infection requires RIG-I and is inhibited by viral C proteins.
    J Virol. 2007 Nov;81(22):12227-37 PMID: 17804509
  12. Hepatitis C virus NS2 and NS3/4A proteins are potent inhibitors of host cell cytokine/chemokine gene expression.
    Virol J. 2006 Sep 01;3:66 PMID: 16945160
  13. SIKE is an IKK epsilon/TBK1-associated suppressor of TLR3- and virus-triggered IRF-3 activation pathways.
    EMBO J. 2005 Dec 7;24(23):4018-28 PMID: 16281057
  14. Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity.
    J Virol. 2008 Jan;82(1):335-45 PMID: 17942531
  15. Double-stranded RNA binding by a heterodimeric complex of murine cytomegalovirus m142 and m143 proteins.
    J Virol. 2006 Oct;80(20):10173-80 PMID: 17005694
  16. Essential role of IRF-3 in lipopolysaccharide-induced interferon-beta gene expression and endotoxin shock.
    Biochem Biophys Res Commun. 2003 Jul 11;306(4):860-6 PMID: 12821121
  17. TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity.
    Nature. 2007 Apr 19;446(7138):916-920 PMID: 17392790
  18. West Nile virus evades activation of interferon regulatory factor 3 through RIG-I-dependent and -independent pathways without antagonizing host defense signaling.
    J Virol. 2006 Mar;80(6):2913-23 PMID: 16501100
  19. Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity.
    Genes Dev. 1998 Jul 1;12(13):2061-72 PMID: 9649509
  20. The Atg5 Atg12 conjugate associates with innate antiviral immune responses.
    Proc Natl Acad Sci U S A. 2007 Aug 28;104(35):14050-5 PMID: 17709747
  21. Loss of DExD/H box RNA helicase LGP2 manifests disparate antiviral responses.
    J Immunol. 2007 May 15;178(10):6444-55 PMID: 17475874
  22. Genome trimming by Borna disease viruses: viral replication control or escape from cellular surveillance?
    Cell Mol Life Sci. 2007 May;64(9):1038-42 PMID: 17372677
  23. Ebola virus VP35 protein binds double-stranded RNA and inhibits alpha/beta interferon production induced by RIG-I signaling.
    J Virol. 2006 Jun;80(11):5168-78 PMID: 16698997
  24. Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways.
    Proc Natl Acad Sci U S A. 2005 Jul 19;102(29):10200-5 PMID: 16009940
  25. Genome trimming: a unique strategy for replication control employed by Borna disease virus.
    Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3441-6 PMID: 15728364
  26. NLRX1 is a regulator of mitochondrial antiviral immunity.
    Nature. 2008 Jan 31;451(7178):573-7 PMID: 18200010
  27. Products of the porcine group C rotavirus NSP3 gene bind specifically to double-stranded RNA and inhibit activation of the interferon-induced protein kinase PKR.
    J Virol. 1994 Jun;68(6):3821-9 PMID: 7514679
  28. Loss of interferon regulatory factor 3 in cells infected with classical swine fever virus involves the N-terminal protease, Npro.
    J Virol. 2005 Jun;79(11):7239-47 PMID: 15890962
  29. Regulation of NF-kappaB signaling by Pin1-dependent prolyl isomerization and ubiquitin-mediated proteolysis of p65/RelA.
    Mol Cell. 2003 Dec;12(6):1413-26 PMID: 14690596
  30. VISA is an adapter protein required for virus-triggered IFN-beta signaling.
    Mol Cell. 2005 Sep 16;19(6):727-40 PMID: 16153868
  31. Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures.
    J Gen Virol. 2008 Jan;89(Pt 1):1-47 PMID: 18089727
  32. Regulation of IkappaB kinase-related kinases and antiviral responses by tumor suppressor CYLD.
    J Biol Chem. 2008 Jul 4;283(27):18621-6 PMID: 18467330
  33. Autophagy and antiviral immunity.
    Curr Opin Immunol. 2008 Feb;20(1):23-9 PMID: 18262399
  34. HIV-1 TAR RNA has an intrinsic ability to activate interferon-inducible enzymes.
    Virology. 1994 Nov 1;204(2):823-7 PMID: 7524241
  35. Recombinant human Metapneumovirus lacking the small hydrophobic SH and/or attachment G glycoprotein: deletion of G yields a promising vaccine candidate.
    J Virol. 2004 Dec;78(23):12877-87 PMID: 15542640
  36. The 5' ends of Hantaan virus (Bunyaviridae) RNAs suggest a prime-and-realign mechanism for the initiation of RNA synthesis.
    J Virol. 1995 Sep;69(9):5754-62 PMID: 7637020
  37. Essential role of mda-5 in type I IFN responses to polyriboinosinic:polyribocytidylic acid and encephalomyocarditis picornavirus.
    Proc Natl Acad Sci U S A. 2006 May 30;103(22):8459-64 PMID: 16714379
  38. The pathogenic NY-1 hantavirus G1 cytoplasmic tail inhibits RIG-I- and TBK-1-directed interferon responses.
    J Virol. 2006 Oct;80(19):9676-86 PMID: 16973572
  39. Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease.
    Science. 2003 May 16;300(5622):1145-8 PMID: 12702807
  40. Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response.
    Nature. 2006 Jan 12;439(7073):208-11 PMID: 16306936
  41. Inhibition of retinoic acid-inducible gene I-mediated induction of beta interferon by the NS1 protein of influenza A virus.
    J Virol. 2007 Jan;81(2):514-24 PMID: 17079289
  42. Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2.
    Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):582-7 PMID: 17190814
  43. Negative feedback regulation of RIG-I-mediated antiviral signaling by interferon-induced ISG15 conjugation.
    J Virol. 2008 Feb;82(3):1474-83 PMID: 18057259
  44. Function of RIG-I-like receptors in antiviral innate immunity.
    J Biol Chem. 2007 May 25;282(21):15315-8 PMID: 17395582
  45. The influenza B virus nonstructural NS1 protein is essential for efficient viral growth and antagonizes beta interferon induction.
    J Virol. 2004 Feb;78(4):1865-72 PMID: 14747551
  46. A20 is a negative regulator of IFN regulatory factor 3 signaling.
    J Immunol. 2005 Feb 1;174(3):1507-12 PMID: 15661910
  47. HHV-8 encoded vIRF-1 represses the interferon antiviral response by blocking IRF-3 recruitment of the CBP/p300 coactivators.
    Oncogene. 2001 Feb 15;20(7):800-11 PMID: 11314014
  48. Negative regulation of interferon-regulatory factor 3-dependent innate antiviral response by the prolyl isomerase Pin1.
    Nat Immunol. 2006 Jun;7(6):598-605 PMID: 16699525
  49. Blockade of interferon induction and action by the E3L double-stranded RNA binding proteins of vaccinia virus.
    J Virol. 2002 May;76(10):5251-9 PMID: 11967338
  50. Autophagy-dependent viral recognition by plasmacytoid dendritic cells.
    Science. 2007 Mar 9;315(5817):1398-401 PMID: 17272685
  51. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3.
    Cell. 2005 Sep 9;122(5):669-82 PMID: 16125763
  52. Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIF.
    Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2992-7 PMID: 15710891
  53. The IRF-3 transcription factor mediates Sendai virus-induced apoptosis.
    J Virol. 2000 Apr;74(8):3781-92 PMID: 10729153
  54. Electrophoretically pure mouse interferon inhibits growth, induces liver and kidney lesions, and kills suckling mice.
    Am J Pathol. 1981 Mar;102(3):396-402 PMID: 6163363
  55. The infected cell protein 0 encoded by bovine herpesvirus 1 (bICP0) induces degradation of interferon response factor 3 and, consequently, inhibits beta interferon promoter activity.
    J Virol. 2007 Apr;81(7):3077-86 PMID: 17215277
  56. Biochemical and genetic evidence for complex formation between the influenza A virus NS1 protein and the interferon-induced PKR protein kinase.
    J Interferon Cytokine Res. 1998 Sep;18(9):757-66 PMID: 9781815
  57. Viral targeting of the interferon-{beta}-inducing Traf family member-associated NF-{kappa}B activator (TANK)-binding kinase-1.
    Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13640-5 PMID: 16155125
  58. Structure of the reovirus outer capsid and dsRNA-binding protein sigma3 at 1.8 A resolution.
    EMBO J. 2001 Mar 1;20(5):979-89 PMID: 11230122
  59. Influenza A virus NS1 protein targets poly(A)-binding protein II of the cellular 3'-end processing machinery.
    EMBO J. 1999 Apr 15;18(8):2273-83 PMID: 10205180
  60. Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity.
    J Immunol. 2005 Sep 1;175(5):2851-8 PMID: 16116171
  61. Influenza A virus NS1 protein prevents activation of NF-kappaB and induction of alpha/beta interferon.
    J Virol. 2000 Dec;74(24):11566-73 PMID: 11090154
  62. The human papillomavirus oncoprotein E7 attenuates NF-kappa B activation by targeting the Ikappa B kinase complex.
    J Biol Chem. 2002 Jul 12;277(28):25576-82 PMID: 11986318
  63. De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling.
    Nature. 2004 Aug 5;430(7000):694-9 PMID: 15258597
  64. Evasion of cellular antiviral responses by human cytomegalovirus TRS1 and IRS1.
    J Virol. 2004 Jan;78(1):197-205 PMID: 14671101
  65. Human metapneumovirus glycoprotein G inhibits innate immune responses.
    PLoS Pathog. 2008 May 30;4(5):e1000077 PMID: 18516301
  66. The NPro product of bovine viral diarrhea virus inhibits DNA binding by interferon regulatory factor 3 and targets it for proteasomal degradation.
    J Virol. 2006 Dec;80(23):11723-32 PMID: 16971436
  67. NLRX1 is a mitochondrial NOD-like receptor that amplifies NF-kappaB and JNK pathways by inducing reactive oxygen species production.
    EMBO Rep. 2008 Mar;9(3):293-300 PMID: 18219313
  68. Disruption of innate immunity due to mitochondrial targeting of a picornaviral protease precursor.
    Proc Natl Acad Sci U S A. 2007 Apr 24;104(17):7253-8 PMID: 17438296
  69. Escape of intracellular Shigella from autophagy.
    Science. 2005 Feb 4;307(5710):727-31 PMID: 15576571
  70. Regulation of antiviral responses by a direct and specific interaction between TRAF3 and Cardif.
    EMBO J. 2006 Jul 26;25(14):3257-63 PMID: 16858409
  71. DUBA: a deubiquitinase that regulates type I interferon production.
    Science. 2007 Dec 7;318(5856):1628-32 PMID: 17991829
  72. A C-terminal basic amino acid motif of Zaire ebolavirus VP35 is essential for type I interferon antagonism and displays high identity with the RNA-binding domain of another interferon antagonist, the NS1 protein of influenza A virus.
    Virology. 2004 Oct 25;328(2):177-84 PMID: 15464838
  73. Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6.
    Nature. 2006 Jan 12;439(7073):204-7 PMID: 16306937
  74. Identification of the rabies virus alpha/beta interferon antagonist: phosphoprotein P interferes with phosphorylation of interferon regulatory factor 3.
    J Virol. 2005 Jun;79(12):7673-81 PMID: 15919920
  75. The primary function of RNA binding by the influenza A virus NS1 protein in infected cells: Inhibiting the 2'-5' oligo (A) synthetase/RNase L pathway.
    Proc Natl Acad Sci U S A. 2006 May 2;103(18):7100-5 PMID: 16627618
  76. Structural and functional analysis of interferon regulatory factor 3: localization of the transactivation and autoinhibitory domains.
    Mol Cell Biol. 1999 Apr;19(4):2465-74 PMID: 10082512
  77. The interferon response circuit: induction and suppression by pathogenic viruses.
    Virology. 2006 Jan 5;344(1):119-30 PMID: 16364743
  78. Autophagy in health and disease: a double-edged sword.
    Science. 2004 Nov 5;306(5698):990-5 PMID: 15528435
  79. IRF3 and IRF7 phosphorylation in virus-infected cells does not require double-stranded RNA-dependent protein kinase R or Ikappa B kinase but is blocked by Vaccinia virus E3L protein.
    J Biol Chem. 2001 Mar 23;276(12):8951-7 PMID: 11124948
  80. The A20 cDNA induced by tumor necrosis factor alpha encodes a novel type of zinc finger protein.
    J Biol Chem. 1990 Sep 5;265(25):14705-8 PMID: 2118515
  81. Inhibition of transcription of the beta interferon gene by the human herpesvirus 6 immediate-early 1 protein.
    J Virol. 2007 Jun;81(11):5737-48 PMID: 17376932
  82. Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages.
    Cell. 2004 Dec 17;119(6):753-66 PMID: 15607973
  83. IFN-regulatory factor 3-dependent gene expression is defective in Tbk1-deficient mouse embryonic fibroblasts.
    Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):233-8 PMID: 14679297
  84. Zinc-binding domain of rotavirus NSP1 is required for proteasome-dependent degradation of IRF3 and autoregulatory NSP1 stability.
    J Gen Virol. 2007 Feb;88(Pt 2):613-620 PMID: 17251580
  85. Lethality of interferon preparations for newborn mice.
    Nature. 1975 Nov 6;258(5530):76-8 PMID: 1186883
  86. Intracellular warfare between human influenza viruses and human cells: the roles of the viral NS1 protein.
    Virology. 2003 May 10;309(2):181-9 PMID: 12758165
  87. Inhibition of PKR activation by the proline-rich RNA binding domain of the herpes simplex virus type 1 Us11 protein.
    J Virol. 2000 Dec;74(23):11215-21 PMID: 11070019
  88. mda-5, but not RIG-I, is a common target for paramyxovirus V proteins.
    Virology. 2007 Mar 1;359(1):190-200 PMID: 17049367
  89. Identification of Ser-386 of interferon regulatory factor 3 as critical target for inducible phosphorylation that determines activation.
    J Biol Chem. 2004 Mar 12;279(11):9698-702 PMID: 14703513
  90. 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. 2004 Dec 7;101(49):17264-9 PMID: 15563593
  91. A20 is a potent inhibitor of TLR3- and Sendai virus-induced activation of NF-kappaB and ISRE and IFN-beta promoter.
    FEBS Lett. 2004 Oct 8;576(1-2):86-90 PMID: 15474016
  92. Human cytomegalovirus TRS1 and IRS1 gene products block the double-stranded-RNA-activated host protein shutoff response induced by herpes simplex virus type 1 infection.
    J Virol. 2005 Jul;79(14):8707-15 PMID: 15994764
  93. Type I interferon [corrected] gene induction by the interferon regulatory factor family of transcription factors.
    Immunity. 2006 Sep;25(3):349-60 PMID: 16979567
  94. Effects of nonstructural proteins NS1 and NS2 of human respiratory syncytial virus on interferon regulatory factor 3, NF-kappaB, and proinflammatory cytokines.
    J Virol. 2005 May;79(9):5353-62 PMID: 15827150
  95. Thogoto virus ML protein suppresses IRF3 function.
    Virology. 2005 Jan 5;331(1):63-72 PMID: 15582653
  96. The C-terminal regulatory domain is the RNA 5'-triphosphate sensor of RIG-I.
    Mol Cell. 2008 Feb 1;29(2):169-79 PMID: 18243112
  97. Expression analysis and genomic characterization of human melanoma differentiation associated gene-5, mda-5: a novel type I interferon-responsive apoptosis-inducing gene.
    Oncogene. 2004 Mar 4;23(9):1789-800 PMID: 14676839
  98. Nonself RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses.
    Mol Cell. 2008 Feb 29;29(4):428-40 PMID: 18242112
  99. IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction.
    Nat Immunol. 2005 Oct;6(10):981-8 PMID: 16127453
  100. RIG-I-mediated antiviral responses to single-stranded RNA bearing 5'-phosphates.
    Science. 2006 Nov 10;314(5801):997-1001 PMID: 17038589
  101. Inhibition of RIG-I-dependent signaling to the interferon pathway during hepatitis C virus expression and restoration of signaling by IKKepsilon.
    J Virol. 2005 Apr;79(7):3969-78 PMID: 15767399
  102. Inhibition of cellular 2'-5' oligoadenylate synthetase by the herpes simplex virus type 1 Us11 protein.
    J Virol. 2007 Apr;81(7):3455-64 PMID: 17229694
  103. Murine cytomegalovirus m142 and m143 are both required to block protein kinase R-mediated shutdown of protein synthesis.
    J Virol. 2006 Oct;80(20):10181-90 PMID: 17005695
  104. Triggering the interferon antiviral response through an IKK-related pathway.
    Science. 2003 May 16;300(5622):1148-51 PMID: 12702806
  105. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses.
    Nat Immunol. 2004 Jul;5(7):730-7 PMID: 15208624
  106. A newly discovered human pneumovirus isolated from young children with respiratory tract disease.
    Nat Med. 2001 Jun;7(6):719-24 PMID: 11385510
  107. Nonstructural proteins NS1 and NS2 of bovine respiratory syncytial virus block activation of interferon regulatory factor 3.
    J Virol. 2003 Aug;77(16):8661-8 PMID: 12885884
  108. Herpes simplex virus 1 has multiple mechanisms for blocking virus-induced interferon production.
    J Virol. 2004 Aug;78(16):8411-20 PMID: 15280450
  109. Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125.
    Proc Natl Acad Sci U S A. 2007 May 1;104(18):7500-5 PMID: 17460044
  110. Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice.
    Science. 2000 Sep 29;289(5488):2350-4 PMID: 11009421
  111. A recombinant influenza A virus expressing an RNA-binding-defective NS1 protein induces high levels of beta interferon and is attenuated in mice.
    J Virol. 2003 Dec;77(24):13257-66 PMID: 14645582
  112. Double-stranded RNA binding of influenza B virus nonstructural NS1 protein inhibits protein kinase R but is not essential to antagonize production of alpha/beta interferon.
    J Virol. 2006 Dec;80(23):11667-77 PMID: 16987984
  113. The RNA helicase Lgp2 inhibits TLR-independent sensing of viral replication by retinoic acid-inducible gene-I.
    J Immunol. 2005 Oct 15;175(8):5260-8 PMID: 16210631
  114. 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 Dec 6;102(49):17717-22 PMID: 16301520
  115. NS1 protein of influenza A virus inhibits the function of intracytoplasmic pathogen sensor, RIG-I.
    Am J Respir Cell Mol Biol. 2007 Mar;36(3):263-9 PMID: 17053203
  116. Coronavirus replication complex formation utilizes components of cellular autophagy.
    J Biol Chem. 2004 Mar 12;279(11):10136-41 PMID: 14699140
  117. IRF-3 activation by Sendai virus infection is required for cellular apoptosis and avoidance of persistence.
    J Virol. 2008 Apr;82(7):3500-8 PMID: 18216110
  118. Processing of genome 5' termini as a strategy of negative-strand RNA viruses to avoid RIG-I-dependent interferon induction.
    PLoS One. 2008 Apr 30;3(4):e2032 PMID: 18446221
  119. Negative regulation of MDA5- but not RIG-I-mediated innate antiviral signaling by the dihydroxyacetone kinase.
    Proc Natl Acad Sci U S A. 2007 Jul 10;104(28):11706-11 PMID: 17600090
  120. The prolyl isomerase Pin1 reveals a mechanism to control p53 functions after genotoxic insults.
    Nature. 2002 Oct 24;419(6909):853-7 PMID: 12397362
  121. Porcine reproductive and respiratory syndrome virus (PRRSV) suppresses interferon-beta production by interfering with the RIG-I signaling pathway.
    Mol Immunol. 2008 May;45(10):2839-46 PMID: 18336912
  122. The prolyl isomerase Pin1 is a regulator of p53 in genotoxic response.
    Nature. 2002 Oct 24;419(6909):849-53 PMID: 12397361
  123. Poxvirus protein N1L targets the I-kappaB kinase complex, inhibits signaling to NF-kappaB by the tumor necrosis factor superfamily of receptors, and inhibits NF-kappaB and IRF3 signaling by toll-like receptors.
    J Biol Chem. 2004 Aug 27;279(35):36570-8 PMID: 15215253
  124. Autophagy defends cells against invading group A Streptococcus.
    Science. 2004 Nov 5;306(5698):1037-40 PMID: 15528445
  125. Identification of human and rat FAD-AMP lyase (cyclic FMN forming) as ATP-dependent dihydroxyacetone kinases.
    Biochem Biophys Res Commun. 2005 Dec 30;338(4):1682-9 PMID: 16289032
  126. The tumour suppressor CYLD is a negative regulator of RIG-I-mediated antiviral response.
    EMBO Rep. 2008 Sep;9(9):930-6 PMID: 18636086
  127. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses.
    Nature. 2006 May 4;441(7089):101-5 PMID: 16625202
  128. Recognition of viruses by innate immunity.
    Immunol Rev. 2007 Dec;220:214-24 PMID: 17979849
  129. 5'-Triphosphate RNA is the ligand for RIG-I.
    Science. 2006 Nov 10;314(5801):994-7 PMID: 17038590
  130. Hepatitis A virus suppresses RIG-I-mediated IRF-3 activation to block induction of beta interferon.
    J Virol. 2005 Sep;79(17):10968-77 PMID: 16103148
  131. Negative regulation of the retinoic acid-inducible gene I-induced antiviral state by the ubiquitin-editing protein A20.
    J Biol Chem. 2006 Jan 27;281(4):2095-103 PMID: 16306043
  132. GB virus B disrupts RIG-I signaling by NS3/4A-mediated cleavage of the adaptor protein MAVS.
    J Virol. 2007 Jan;81(2):964-76 PMID: 17093192
  133. Virus-dependent phosphorylation of the IRF-3 transcription factor regulates nuclear translocation, transactivation potential, and proteasome-mediated degradation.
    Mol Cell Biol. 1998 May;18(5):2986-96 PMID: 9566918
  134. TLR-dependent and TLR-independent pathways of type I interferon induction in systemic autoimmunity.
    Nat Med. 2007 May;13(5):543-51 PMID: 17479100
  135. The mengovirus leader protein blocks interferon-alpha/beta gene transcription and inhibits activation of interferon regulatory factor 3.
    Cell Microbiol. 2007 Dec;9(12):2921-30 PMID: 17991048
  136. The Bovine herpesvirus 1 gene encoding infected cell protein 0 (bICP0) can inhibit interferon-dependent transcription in the absence of other viral genes.
    J Gen Virol. 2005 Oct;86(Pt 10):2697-2702 PMID: 16186222
  137. IFNbeta induction by influenza A virus is mediated by RIG-I which is regulated by the viral NS1 protein.
    Cell Microbiol. 2007 Apr;9(4):930-8 PMID: 17140406
  138. The roles of two IkappaB kinase-related kinases in lipopolysaccharide and double stranded RNA signaling and viral infection.
    J Exp Med. 2004 Jun 21;199(12):1641-50 PMID: 15210742
  139. Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus.
    Nature. 2005 Oct 20;437(7062):1167-72 PMID: 16177806
  140. IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway.
    Nat Immunol. 2003 May;4(5):491-6 PMID: 12692549
  141. Mutant influenza viruses with a defective NS1 protein cannot block the activation of PKR in infected cells.
    J Virol. 1999 Mar;73(3):2425-33 PMID: 9971827
Article Info
Journal
Cytokine
Abbr.
Cytokine
ISSN
1096-0023
DOI
10.1016/j.cyto.2008.07.011
Published
2008-09-00
Epub
2008-00-13
Pages
350-8
Language
English
Region
England
NLM ID
9005353
PMCID
PMC2575845
Subset
IM
Grants
NIAID NIH HHS · R01 AI073919 · United States
NIAID NIH HHS · R21 AI077020 · United States
NIAID NIH HHS · R21 AI077020-01 · United States
NIAID NIH HHS · R21 AI077020-02 · United States
NIAID NIH HHS · R01 AI050707 · United States
NIAID NIH HHS · R01 AI050707-07A1 · United States
NIAID NIH HHS · R01 AI050707-06 · United States
NIAID NIH HHS · R01 AI073919-01A1 · United States
External Links
PubMed source DOI: 10.1016/j.cyto.2008.07.011 PMC Full Text View journal details
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