Regulation of antiviral innate immune signaling and viral evasion following viral genome sensing

다국어 초록 (Multilingual Abstract)

A harmonized balance between positive and negative regulation of pattern recognition receptor (PRR)-initiated immune responses is required to achieve the most favorable outcome for the host. This balance is crucial because it must not only ensure activation of the first line of defense against viral infection but also prevent inappropriate immune activation, which results in autoimmune diseases. Recent studies have shown how signal transduction pathways initiated by PRRs are positively and negatively regulated by diverse modulators to maintain host immune homeostasis. However, viruses have developed strategies to subvert the host antiviral response and establish infection. Viruses have evolved numerous genes encoding immunomodulatory proteins that antagonize the host immune system. This review focuses on the current state of knowledge regarding key host factors that regulate innate immune signaling molecules upon viral infection and discusses evidence showing how specific viral proteins counteract antiviral responses via immunomodulatory strategies.

참고문헌 (Reference)

1 Du, J., "pVHL Negatively Regulates Antiviral Signaling by Targeting MAVS for Proteasomal Degradation" 195 : 1782-1790, 2015

2 Chen, Y., "p38 inhibition provides anti-DNA virus immunity by regulation of USP21 phosphorylation and STING activation" 214 : 991-1010, 2017

3 Luo, W. W., "iRhom2 is essential for innate immunity to DNA viruses by mediating trafficking and stability of the adaptor STING" 17 : 1057-1066, 2016

4 Ablasser, A., "cGAS produces a 2’-5’-linked cyclic dinucleotide second messenger that activates STING" 498 : 380-384, 2013

5 Song, T., "c-Abl tyrosine kinase interacts with MAVS and regulates innate immune response" 584 : 33-38, 2010

6 Lin, S., "Zika virus NS5 protein antagonizes type I interferon production via blocking TBK1 activation" 527 : 180-187, 2019

7 Zhu, K., "WDR82 negatively regulates cellular antiviral response by mediating TRAF3 polyubiquitination in multiple cell lines" 195 : 5358-5366, 2015

8 Bridgeman, A., "Viruses transfer the antiviral second messenger cGAMP between cells" 349 : 1228-1232, 2015

9 Mao, A. P., "Virus-triggered ubiquitination of TRAF3/6 by cIAP1/2 is essential for induction of interferon-beta(IFN-beta)and cellular antiviral response" 285 : 9470-9476, 2010

10 Onoguchi, K., "Virus-infection or 5’ppp-RNA activates antiviral signal through redistribution of IPS-1 mediated by MFN1" 6 : e1001012-, 2010

11 Lin, R., "Virus-dependent phosphorylation of the IRF-3 transcription factor regulates nuclear translocation, transactivation potential, and proteasome-mediated degradation" 18 : 2986-2996, 1998

12 Schröder, M., "Viral targeting of DEAD box protein 3reveals its role in TBK1/IKKepsilon-mediated IRF activation" 27 : 2147-2157, 2008

13 Ning, Y. J., "Viral suppression of innate immunity via spatial isolation of TBK1/IKKε from mitochondrial antiviral platform" 6 : 324-337, 2014

14 Chan, Y. K., "Viral evasion of intracellular DNA and RNA sensing" 14 : 360-373, 2016

15 Eaglesham, J. B., "Viral and metazoan poxins are cGAMP-specific nucleases that restrict cGAS-STING signalling" 566 : 259-263, 2019

16 Zhu, H., "Varicella-zoster virus immediate-early protein ORF61 abrogates the IRF3-mediated innate immune response through degradation of activated IRF3" 85 : 11079-11089, 2011

17 Sen, N., "Varicella-zoster virus immediate-early protein 62 blocks interferon regulatory factor 3(IRF3)phosphorylation at key serine residues : a novel mechanism of IRF3 inhibition among herpesviruses" 84 : 9240-9253, 2010

18 Xu, L. G., "VISA is an adapter protein required for virus-triggered IFN-beta signaling" 19 : 727-740, 2005

19 Mowen, K. A., "Unconventional post-translational modifications in immunological signaling" 15 : 512-520, 2014

20 Ni, G., "Ubiquitination of STING at lysine 224 controls IRF3 activation" 2 : eaah7119-, 2017

21 Zhang, L., "Ubiquitin-specific protease 2b negatively regulates IFN-β production and antiviral activity by targeting TANKbinding kinase 1" 193 : 2230-2237, 2014

22 Huang, L., "Ubiquitin-conjugating enzyme 2S enhances viral replication by inhibiting type I IFN production through recruiting USP15 to deubiquitinate TBK1" 32 : 108044-, 2020

23 Ye, L., "USP49 negatively regulates cellular antiviral responses via deconjugating K63-linked ubiquitination of MITA" 15 : e1007680-, 2019

24 Zhang, H. Y., "USP44 positively regulates innate immune response to DNA viruses through deubiquitinating MITA" 16 : e1008178-, 2020

25 Lin, M., "USP38 inhibits Type I interferon signaling by editing TBK1 ubiquitination through NLRP4 signalosome" 64 : 267-281, 2016

26 Cai, Z., "USP22 promotes IRF3 nuclear translocation and antiviral responses by deubiquitinating the importin protein KPNA2" 217 : e20191174-, 2020

27 Zhang, M. X., "USP20 promotes cellular antiviral responses via deconjugating K48-linked ubiquitination of MITA" 202 : 2397-2406, 2019

28 Gu, Z., "USP19 suppresses cellular type I interferon signaling by targeting TRAF3 for deubiquitination" 12 : 767-779, 2017

29 Zhang, M., "USP18 recruits USP20 to promote innate antiviral response through deubiquitinating STING/MITA" 26 : 1302-1319, 2016

30 Sun, H., "USP13 negatively regulates antiviral responses by deubiquitinating STING" 8 : 15534-, 2017

31 Yu, Z., "USP1-UAF1 deubiquitinase complex stabilizes TBK1 and enhances antiviral responses" 214 : 3553-3563, 2017

32 Yang, L., "UBXN3B positively regulates STING-mediated antiviral immune responses" 9 : 2329-, 2018

33 Wang, P., "UBXN1 interferes with Rig-I-like receptor-mediated antiviral immune response by targeting MAVS" 3 : 1057-1070, 2013

34 Chen, T., "UBQLN2 Promotes the production of type I interferon via the TBK1-IRF3 PAthway" 9 : 1205-, 2020

35 Moriyama, M., "Two conserved amino acids within the NSs of severe fever with thrombocytopenia syndrome phlebovirus are essential for anti-interferon activity" 92 : e00706-18, 2018

36 Arch, R. H., "Tumor necrosis factor receptorassociated factors(TRAFs)-a family of adapter proteins that regulates life and death" 12 : 2821-2830, 1998

37 Inoue, J., "Tumor necrosis factor receptor-associated factor(TRAF)family : adapter proteins that mediate cytokine signaling" 254 : 14-24, 2000

38 Liang, Q., "Tripartite motif-containing protein 28 is a small ubiquitin-related modifier E3 ligase and negative regulator of IFN regulatory factor 7" 187 : 4754-4763, 2011

39 Gentili, M., "Transmission of innate immune signaling by packaging of cGAMP in viral particles" 349 : 1232-1236, 2015

40 Zhou, C., "Transfer of cGAMP into bystander cells via LRRC8 volumeregulated anion channels augments STING-mediated interferon responses and anti-viral immunity" 52 : 767-781, 2020

41 Jennings, S., "Thogoto virus ML protein suppresses IRF3 function" 331 : 63-72, 2005

42 Vandevenne, P., "The varicella-zoster virus ORF47 kinase interferes with host innate immune response by inhibiting the activation of IRF3" 6 : e16870-, 2011

43 Oshiumi, H., "The ubiquitin ligase Riplet is essential for RIG-I-dependent innate immune responses to RNA virus infection" 8 : 496-509, 2010

44 Zhong, B., "The ubiquitin ligase RNF5 regulates antiviral responses by mediating degradation of the adaptor protein MITA" 30 : 397-407, 2009

45 Komander, D., "The ubiquitin code" 81 : 203-229, 2012

46 Liu, B., "The ubiquitin E3 ligase TRIM31 promotes aggregation and activation of the signaling adaptor MAVS through Lys63-linked polyubiquitination" 18 : 214-224, 2017

47 Yu, Y., "The ubiquitin E3 ligase RAUL negatively regulates type i interferon through ubiquitination of the transcription factors IRF7 and IRF3" 33 : 863-877, 2010

48 Li, X., "The tyrosine kinase Src promotes phosphorylation of the kinase TBK1to facilitate type I interferon production after viral infection" 10 : aae0435-, 2017

49 Friedman, C. S., "The tumour suppressor CYLD is a negative regulator of RIGI-mediated antiviral response" 9 : 930-936, 2008

50 Pang, L. L., "The suppression of innate immune response by human rhinovirus C" 490 : 22-28, 2017

51 Beachboard, D. C., "The small GTPase RAB1B promotes antiviral innate immunity by interacting with TNF receptor-associated factor 3(TRAF3)" 294 : 14231-14240, 2019

52 Dempsey, P. W., "The signaling adaptors and pathways activated by TNF superfamily" 14 : 193-209, 2003

53 Hemmi, H., "The roles of two IkappaB kinase-related kinases in lipopolysaccharide and double stranded RNA signaling and viral infection" 199 : 1641-1650, 2004

54 Jiang, X., "The role of ubiquitylation in immune defence and pathogen evasion" 12 : 35-48, 2011

55 Liu, C., "The otubain YOD1 suppresses aggregation and activation of the signaling adaptor MAVS through Lys63-linked deubiquitination" 202 : 2957-2970, 2019

56 Yoo, Y. S., "The mitochondrial ubiquitin ligase MARCH5 resolves MAVS aggregates during antiviral signalling" 6 : 7910-, 2015

57 Wang, C., "The methyltransferase NSD3 promotes antiviral innate immunity via direct lysine methylation of IRF3" 214 : 3597-3610, 2017

58 Ding, B., "The matrix protein of human parainfluenza virus type 3 induces mitophagy that suppresses interferon responses" 21 : 538-547, 2017

59 Wang, D., "The leader proteinase of foot-and-mouth disease virus negatively regulates the type I interferon pathway by acting as a viral deubiquitinase" 85 : 3758-3766, 2011

60 Zhou, Y., "The kinase CK1ɛ controls the antiviral immune response by phosphorylating the signaling adaptor TRAF3" 17 : 397-405, 2016

61 Negishi, H., "The interferon(IFN)class of cytokines and the IFN regulatory factor(IRF)transcription factor family" 10 : a028423-, 2018

62 Bruns, A. M., "The innate immune sensor LGP2 activates antiviral signaling by regulating MDA5-RNA interaction and filament assembly" 55 : 771-781, 2014

63 Diner, E. J., "The innate immune DNA sensor cGAS produces a noncanonical cyclic dinucleotide that activates human STING" 3 : 1355-1361, 2013

64 Saira, K., "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" 81 : 3077-3086, 2007

65 Yau, R., "The increasing complexity of the ubiquitin code" 18 : 579-586, 2016

66 Stempel, M., "The herpesviral antagonist m152 reveals differential activation of STING-dependent IRF and NF-κB signaling and STING’s dual role during MCMV infection" 38 : e100983-, 2019

67 Wei, C., "The hepatitis B virus X protein disrupts innate immunity by downregulating mitochondrial antiviral signaling protein" 185 : 1158-1168, 2010

68 Zhang, L., "The deubiquitinase CYLD is a specific checkpoint of the STING antiviral signaling pathway" 14 : e1007435-, 2018

69 Mukherjee, A., "The coxsackievirus B 3C protease cleaves MAVS and TRIF to attenuate host type I interferon and apoptotic signaling" 7 : e1001311-, 2011

70 Cai, X., "The cGAS-cGAMP-STING pathway of cytosolic DNA sensing and signaling" 54 : 289-296, 2014

71 Matthews, K., "The SARS coronavirus papain like protease can inhibit IRF3 at a post activation step that requires deubiquitination activity" 11 : 209-, 2014

72 Zhao, T., "The NEMO adaptor bridges the nuclear factor-kappaB and interferon regulatory factor signaling pathways" 8 : 592-600, 2007

73 Yu, Y., "The KSHV immediate-early transcription factor RTA encodes ubiquitin E3 ligase activity that targets IRF7 for proteosomemediated degradation" 22 : 59-70, 2005

74 Nakhaei, P., "The E3 ubiquitin ligase Triad3A negatively regulates the RIG-I/MAVS signaling pathway by targeting TRAF3 for degradation" 5 : e1000650-, 2009

75 Higgs, R., "The E3 ubiquitin ligase Ro52 negatively regulates IFN-beta production post-pathogen recognition by polyubiquitin-mediated degradation of IRF3" 181 : 1780-1786, 2008

76 Wang, C., "The E3 ubiquitin ligase Nrdp1 ‘preferentially’ promotes TLRmediated production of type I interferon" 10 : 744-752, 2009

77 Wang, Q., "The E3 ubiquitin ligase AMFR and INSIG1 bridge the activation of TBK1 kinase by modifying the adaptor STING" 41 : 919-933, 2014

78 Gray, E. E., "The AIM2-like receptors are dispensable for the interferon response to intracellular DNA" 45 : 255-266, 2016

79 Ning, S., "The A20 deubiquitinase activity negatively regulates LMP1 activation of IRF7" 84 : 6130-6138, 2010

80 Jin, S., "Tetherin suppresses type I interferon signaling by targeting MAVS for NDP52-mediated selective autophagic degradation in human cells" 68 : 308-322, 2017

81 García-Sastre, A., "Ten Strategies of Interferon Evasion by Viruses" 22 : 176-184, 2017

82 Ju, L. G., "TTLL12 inhibits the activation of cellular antiviral signaling through interaction with VISA/MAVS" 198 : 1274-1284, 2017

83 Qin, Y., "TRIM9 short isoform preferentially promotes DNA and RNA virusinduced production of type I interferon by recruiting GSK3β to TBK1" 26 : 613-628, 2016

84 Sun, N., "TRIM35 mediates protection against influenza infection by activating TRAF3 and degrading viral PB2" 11 : 894-914, 2020

85 Wang, Y., "TRIM30α is a negative-feedback regulator of the intracellular DNA and DNA virus-triggered response by targeting STING" 11 : e1005012-, 2015

86 Li, Q., "TRIM29 negatively controls antiviral immune response through targeting STING for degradation" 4 : 13-, 2018

87 Wang, P., "TRIM26 negatively regulates interferon-β production and antiviral response through polyubiquitination and degradation of nuclear IRF3" 11 : e1004726-, 2015

88 Zhu, Q., "TRIM24 facilitates antiviral immunity through mediating K63-linked TRAF3 ubiquitination" 217 : e20192083-, 2020

89 Xue, B., "TRIM21 promotes innate immune response to RNA viral infection through Lys27-linked polyubiquitination of MAVS" 92 : e00321-18, 2018

90 Ning, S., "TRAF6 and the three C-terminal lysine sites on IRF7 are required for its ubiquitination-mediated activation by the tumor necrosis factor receptor family member latent membrane protein 1" 28 : 6536-6546, 2008

91 Zhang, M., "TRAF-interacting protein(TRIP)negatively regulates IFN-βproduction and antiviral response by promoting proteasomal degradation of TANK-binding kinase 1" 209 : 1703-1711, 2012

92 Sun, M. S., "TMED2 potentiates cellular IFN responses to DNA viruses by reinforcing MITA dimerization and facilitating Its trafficking" 25 : 3086-3098, 2018

93 He, T. S., "THO complex subunit 7 homolog negatively regulates cellular antiviral response against RNA. Viruses Target. TBK1" 11 : 158-, 2019

94 Choi, Y. B., "TAX1BP1 restrains virus-induced apoptosis by facilitating itch-mediated degradation of the mitochondrial adaptor MAVS" 37 : e00422-, 2017

95 Parvatiyar, K., "TAX1BP1 and A20 inhibit antiviral signaling by targeting TBK1-IKKi kinases" 285 : 14999-15009, 2010

96 Yuen, C. K., "Suppression of type I interferon production by human T-cell leukemia virus type 1 oncoprotein tax through inhibition of IRF3 phosphorylation" 90 : 3902-3912, 2016

97 Tu, D., "Structure and ubiquitination-dependent activation of TANK-binding kinase 1" 3 : 747-758, 2013

98 Kato, K., "Structural insights into cGAMP degradation by ecto-nucleotide pyrophosphatase phosphodiesterase 1" 9 : 4424-, 2018

99 Ergun, S. L., "Structural insights into STING signaling" 30 : 399-407, 2020

100 Zhang, C., "Structural basis of STING binding with and phosphorylation by TBK1" 567 : 394-398, 2019

101 Vijayan, M., "Sphingosine 1-phosphate lyase enhances the activation of IKKεto promote type I IFN-mediated innate immune responses to influenza A virus infection" 199 : 677-687, 2017

102 Pawson, T., "Specificity in signal transduction : from phosphotyrosine-SH2 domain interactions to complex cellular systems" 116 : 191-203, 2004

103 Zheng, Q., "Siglec1 suppresses antiviral innate immune response by inducing TBK1 degradation via the ubiquitin ligase TRIM27" 25 : 1121-1136, 2015

104 Yoneyama, M., "Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity" 175 : 2851-2858, 2005

105 Siu, K. L., "Severe acute respiratory syndrome coronavirus M protein inhibits type I interferon production by impeding the formation of TRAF3.TANK.TBK1/IKKepsilon complex" 284 : 16202-16209, 2009

106 Zheng, Y., "Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)membrane(M)protein inhibits type I and III interferon production by targeting RIG-I/MDA-5 signaling" 5 : 299-, 2020

107 Takahasi, K., "Ser386 phosphorylation of transcription factor IRF-3 induces dimerization and association with CBP/p300 without overall conformational change" 15 : 901-910, 2010

108 Qian, S., "Seneca valley virus suppresses host type I interferon production by targeting adaptor proteins MAVS, TRIF, and TANK for cleavage" 91 : e00823-17, 2017

109 Xue, Q., "Seneca Valley Virus 3C(pro)abrogates the IRF3-and IRF7-mediated innate immune response by degrading IRF3 and IRF7" 518 : 1-7, 2018

110 Higgs, R., "Self protection from anti-viral responses-Ro52 promotes degradation of the transcription factor IRF7 downstream of the viral Toll-Like receptors" 5 : e11776-, 2010

111 Xie, M., "Scavenger receptor A impairs interferon response to HBV infection by limiting TRAF3 ubiquitination through recruiting OTUB1" 287 : 310-324, 2020

112 Hiller, B., "STING signaling the enERGIC way" 18 : 137-139, 2015

113 Ishikawa, H., "STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity" 461 : 788-792, 2009

114 Hansen, A. L., "STING palmitoylation as a therapeutic target" 16 : 236-241, 2019

115 Ishikawa, H., "STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling" 455 : 674-678, 2008

116 Burdette, D. L., "STING and the innate immune response to nucleic acids in the cytosol" 14 : 19-26, 2013

117 Wei, J., "SNX8 modulates innate immune response to DNA virus by mediating trafficking and activation of MITA" 14 : e1007336-, 2018

118 Ran, Y., "SENP2 negatively regulates cellular antiviral response by deSUMOylating IRF3 and conditioning it for ubiquitination and degradation" 3 : 283-292, 2011

119 Shi, C. S., "SARS-coronavirus open reading frame-9b suppresses innate immunity by targeting mitochondria and the MAVS/TRAF3/TRAF6 signalosome" 193 : 3080-3089, 2014

120 Moustaqil, M., "SARS-CoV-2 proteases PLpro and 3CLpro cleave IRF3 and critical modulators of inflammatory pathways(NLRP12 and TAB1) : implications for disease presentation across species" 10 : 178-195, 2021

121 Wang, W., "SARS-CoV-2 nsp12 attenuates type I interferon production by inhibiting IRF3 nuclear translocation" 18 : 945-953, 2021

122 Guo, G., "SARS-CoV-2 non-structural protein 13(nsp13)hijacks host deubiquitinase USP13 and counteracts host antiviral immune response" 6 : 119-, 2021

123 Fu, Y. Z., "SARS-CoV-2 membrane glycoprotein M antagonizes the MAVSmediated innate antiviral response" 18 : 613-620, 2020

124 Fung, S. Y., "SARS-CoV-2 main protease suppresses type I interferon production by preventing nuclear translocation of phosphorylated IRF3" 17 : 1547-1554, 2021

125 Wu, J., "SARS-CoV-2 ORF9b inhibits RIG-I-MAVS antiviral signaling by interrupting K63-linked ubiquitination of NEMO" 34 : 108761-, 2021

126 Chen, X., "SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex" 5 : 369-381, 2014

127 Kim, J. H., "Rubicon modulates antiviral type I interferon(IFN)signaling by targeting IFN regulatory factor 3 dimerization" 91 : e00248-17, 2017

128 Barro, M., "Rotavirus nonstructural protein 1 subverts innate immune response by inducing degradation of IFN regulatory factor 3" 102 : 4114-4119, 2005

129 Ding, S., "Rotavirus VP3 targets MAVS for degradation to inhibit type III interferon expression in intestinal epithelial cells" 7 : e39494-, 2018

130 Arnold, M. M., "Rotavirus NSP1 mediates degradation of interferon regulatory factors through targeting of the dimerization domain" 87 : 9813-9821, 2013

131 Durand, J. K., "Roles for the IKK-related kinases TBK1and IKKε in cancer" 7 : 139-, 2018

132 Kuo, R. L., "Role of N terminus-truncated NS1 proteins of influenza A virus in inhibiting IRF3 activation" 90 : 4696-4705, 2016

133 Chen, H. W., "Ring finger protein 166 potentiates RNA virus-induced interferon-β production via enhancing the ubiquitination of TRAF3 and TRAF6" 5 : 14770-, 2015

134 Boyapalle, S., "Respiratory syncytial virus NS1 protein colocalizes with mitochondrial antiviral signaling protein MAVS following infection" 7 : e29386-, 2012

135 Ben-Neriah, Y., "Regulatory functions of ubiquitination in the immune system" 3 : 20-26, 2002

136 Li, S., "Regulation of virus-triggered signaling by OTUB1-and OTUB2-mediated deubiquitination of TRAF3 and TRAF6" 285 : 4291-4297, 2010

137 Ivashkiv, L. B., "Regulation of type I interferon responses" 14 : 36-49, 2014

138 Häcker, H., "Regulation and function of IKK and IKK-related kinases" 2006 : re13-, 2006

139 Long, L., "Recruitment of phosphatase PP2A by RACK1 adaptor protein deactivates transcription factor IRF3 and limits type I interferon signaling" 40 : 515-529, 2014

140 Yang, B., "RNF90 negatively regulates cellular antiviral responses by targeting MITA for degradation" 16 : e1008387-, 2020

141 Zhang, Z. D., "RNF115 plays dual roles in innate antiviral responses by catalyzing distinct ubiquitination of MAVS and MITA" 11 : 5536-, 2020

142 Komuro, A., "RNA-and virus-independent inhibition of antiviral signaling by RNA helicase LGP2" 80 : 12332-12342, 2006

143 Yoneyama, M., "RNA recognition and signal transduction by RIG-I-like receptors" 227 : 54-65, 2009

144 Zan, J., "RNA helicase DDX5 suppresses IFN-I antiviral innate immune response by interacting with PP2A-Cβ to deactivate IRF3" 396 : 112332-, 2020

145 Gu, M., "RKIP and TBK1 form a positive feedback loop to promote type I interferon production in innate immunity" 35 : 2553-2565, 2016

146 Wu, X., "RIG-I and IL-6 are negative-feedback regulators of STING induced by double-stranded DNA" 12 : e0182961-, 2017

147 Agbowuro, A. A., "Proteases and protease inhibitors in infectious diseases" 38 : 1295-1331, 2018

148 Zhou, Y., "Post-translational regulation of antiviral innate signaling" 47 : 1414-1426, 2017

149 Deribe, Y. L., "Post-translational modifications in signal integration" 17 : 666-672, 2010

150 Liu, J., "Post-translational modification control of innate immunity" 45 : 15-30, 2016

151 Dawson, A. R., "Post-translation regulation of influenza virus replication" 11 : 517461-, 2020

152 Uchida, S., "Possible role of the Nipah virus V protein in the regulation of the interferon beta induction by interacting with UBX domain-containing protein1" 8 : 7682-, 2018

153 Sato, M., "Positive feedback regulation of type I IFN genes by the IFNinducible transcription factor IRF-7" 441 : 106-110, 1998

154 Huang, C., "Porcine reproductive and respiratory syndrome virus nonstructural protein 4 antagonizes beta interferon expression by targeting the NFκB essential modulator" 88 : 10934-10945, 2014

155 Beura, L. K., "Porcine reproductive and respiratory syndrome virus nonstructural protein 1beta modulates host innate immune response by antagonizing IRF3 activation" 84 : 1574-1584, 2010

156 Dong, J., "Porcine reproductive and respiratory syndrome virus 3C protease cleaves the mitochondrial antiviral signalling complex to antagonize IFN-βexpression" 96 : 3049-3058, 2015

157 Li, Z., "Porcine haemagglutinating encephalomyelitis virus deactivates transcription factor IRF3 and limits type I interferon production" 252 : 108918-, 2021

158 Ding, Z., "Porcine epidemic diarrhea virus nucleocapsid protein antagonizes beta interferon production by sequestering the interaction between IRF3 and TBK1" 88 : 8936-8945, 2014

159 Wu, Y., "Porcine epidemic diarrhea virus nsp15 antagonizes interferon signaling by RNA degradation of TBK1 and IRF3" 12 : 599-, 2020

160 Wang, D., "Porcine epidemic diarrhea virus 3C-like protease regulates its interferon antagonism by cleaving NEMO" 90 : 2090-2101, 2016

161 Zhu, X., "Porcine deltacoronavirus nsp5 inhibits interferon-β production through the cleavage of NEMO" 502 : 33-38, 2017

162 Arimoto, K., "Polyubiquitin conjugation to NEMO by triparite motif protein 23(TRIM23)is critical in antiviral defense" 107 : 15856-15861, 2010

163 Zhou, X., "Poly(C)-binding protein 1(PCBP1)mediates housekeeping degradation of mitochondrial antiviral signaling(MAVS)" 22 : 717-727, 2012

164 Vitour, D., "Polo-like kinase 1(PLK1)regulates interferon(IFN)induction by MAVS" 284 : 21797-21809, 2009

165 Liu, S., "Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation" 347 : aaa2630-, 2015

166 Li, S. Z., "Phosphorylation of MAVS/VISA by nemo-like kinase(NLK)for degradation regulates the antiviral innate immune response" 10 : 3233-, 2019

167 Zhan, Z., "Phosphatase PP4 negatively regulates type I IFN production and antiviral innate immunity by dephosphorylating and deactivating TBK1" 195 : 3849-3857, 2015

168 Qi, D., "Phosphatase Cdc25A negatively regulates the antiviral immune response by inhibiting TBK1 activity" 92 : e01118-18, 2018

169 Zhu, Z., "Peste des petits ruminants virus nucleocapsid protein inhibits beta interferon production by interacting with IRF3 to block its activation" 93 : e00362-19, 2019

170 Dixit, E., "Peroxisomes are signaling platforms for antiviral innate immunity" 141 : 668-681, 2010

171 Mogensen, T. H., "Pathogen recognition and inflammatory signaling in innate immune defenses" 22 : 240-273, 2009

172 Xin, D., "Parkin negatively regulates the antiviral signaling pathway by targeting TRAF3 for degradation" 293 : 11996-12010, 2018

173 Xia, T., "PTPN1/2-mediated dephosphorylation of MITA/STING promotes its 20S proteasomal degradation and attenuates innate antiviral response" 116 : 20063-20069, 2019

174 Zhao, Y., "PPM1B negatively regulates antiviral response via dephosphorylating TBK1" 24 : 2197-2204, 2012

175 Xiang, W., "PPM1A silences cytosolic RNA sensing and antiviral defense through direct dephosphorylation of MAVS and TBK1" 2 : e1501889-, 2016

176 Li, Z., "PPM1A regulates antiviral signaling by antagonizing TBK1-mediated STING phosphorylation and aggregation" 11 : e1004783-, 2015

177 Wang, G., "PLP2 of mouse hepatitis virus A59(MHV-A59)targets TBK1 to negatively regulate cellular type I interferon signaling pathway" 6 : e17192-, 2011

178 Gao, X., "PLA1A participates in the antiviral innate immune response by facilitating the recruitment of TANK-binding kinase 1 to mitochondria" 10 : 315-327, 2018

179 You, F., "PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiquitin ligase AIP4" 10 : 1300-1308, 2009

180 Cao, L., "P200 family protein IFI204 negatively regulates type I interferon responses by targeting IRF7 in nucleus" 15 : e1008079-, 2019

181 Frias-Staheli, N., "Ovarian tumor domain-containing viral proteases evade ubiquitin-and ISG15-dependent innate immune responses" 2 : 404-416, 2007

182 Guo, Y., "OTUD5 promotes innate antiviral and antitumor immunity through deubiquitinating and stabilizing STING" 1 : 11-, 2020

183 Zhang, Z., "OTUD1 negatively regulates type I IFN induction by disrupting noncanonical ubiquitination of IRF3" 204 : 1904-1918, 2020

184 Li, T., "O-GlcNAc transferase links glucose metabolism to MAVS-mediated antiviral innate immunity" 24 : 791-803, 2018

185 Dunphy, G., "Non-canonical activation of the DNA sensing adaptor STING by ATM and IFI16 mediates NF-κB signaling after nuclear DNA damage" 71 : 745-760, 2018

186 Arimoto, K., "Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125" 104 : 7500-7505, 2007

187 Refolo, G., "Negative regulation of mitochondrial antiviral signaling proteinmediated antiviral signaling by the mitochondrial protein LRPPRC during hepatitis C virus infection" 69 : 34-50, 2019

188 Saitoh, T., "Negative regulation of interferon-regulatory factor 3-dependent innate antiviral response by the prolyl isomerase Pin1" 7 : 598-605, 2006

189 Wang, J., "Negative regulation of Nmi on virus-triggered type I IFN production by targeting IRF7" 191 : 3393-3399, 2013

190 Chathuranga, K., "Negative regulation of NEMO signaling by the ubiquitin E3ligase MARCH2" 39 : e105139-, 2020

191 Jia, Y., "Negative regulation of MAVS-mediated innate immune response by PSMA7" 183 : 4241-4248, 2009

192 Han, Y., "Negative regulation of MAVS-mediated innate immune response by ASC" 445 : 35-43, 2018

193 Liang, Q., "Negative regulation of IRF7 activation by activating transcription factor 4 suggests a cross-regulation between the IFN responses and the cellular integrated stress responses" 186 : 1001-1010, 2011

194 Lee, K. J., "Negative regulation of IKKε-mediated IRF7 phosphorylation by HSP70" 204 : 2562-2574, 2020

195 Zhang, M., "Negative feedback regulation of cellular antiviral signaling by RBCK1-mediated degradation of IRF3" 18 : 1096-1104, 2008

196 Wang, Y., "Ndfip1 negatively regulates RIG-I-dependent immune signaling by enhancing E3 ligase Smurf1-mediated MAVS degradation" 189 : 5304-5313, 2012

197 Guo, H., "NLRX1 sequesters STING to negatively regulate the interferon response, thereby facilitating the replication of HIV-1 and DNA viruses" 19 : 515-528, 2016

198 Qin, Y., "NLRX1 mediates MAVS degradation to attenuate the hepatitis C virus-induced innate immune response through PCBP2" 91 : e01264-17, 2017

199 Cui, J., "NLRP4 negatively regulates type I interferon signaling by targeting the kinase TBK1 for degradation via the ubiquitin ligase DTX4" 13 : 387-395, 2012

200 Yang, Y., "NLRP2 negatively regulates antiviral immunity by interacting with TBK1" 48 : 1817-1825, 2018

201 Pomerantz, J. L., "NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase" 18 : 6694-6704, 1999

202 Wang, L., "NEMO binds ubiquitinated TANK-binding kinase 1(TBK1)to regulate innate immune responses to RNA viruses" 7 : e43756-, 2012

203 Xia, Z., "NAC1 potentiates cellular antiviral signaling by bridging MAVS and TBK1" 203 : 1001-1011, 2019

204 Kang, H. R., "Murine gammaherpesvirus 68 encoding open reading frame 11targets TANK binding kinase 1 to negatively regulate the host type I interferon response" 88 : 6832-6846, 2014

205 Meng, F., "Mst1 shuts off cytosolic antiviral defense through IRF3 phosphorylation" 30 : 1086-1100, 2016

206 Ma, X., "Molecular basis of Tank-binding kinase 1 activation by transautophosphorylation" 109 : 9378-9383, 2012

207 Ma, Z., "Modulation of the cGAS-STING DNA sensing pathway by gammaherpesviruses" 112 : E4306-E4315, 2015

208 Yasukawa, K., "Mitofusin 2 inhibits mitochondrial antiviral signaling" 2 : ra47-, 2009

209 Horner, S. M., "Mitochondrialassociated endoplasmic reticulum membranes (MAM) form innate immune synapses and are targeted by hepatitis C virus" 108 : 14590-14595, 2011

210 Wong, L. R., "Middle east respiratory syndrome coronavirus ORF8b accessory protein suppresses type I IFN expression by impeding HSP70-dependent activation of IRF3 kinase IKKε" 205 : 1564-1579, 2020

211 Lui, P. Y., "Middle East respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3" 5 : e39-, 2016

212 Li, X., "Methyltransferase Dnmt3a upregulates HDAC9 to deacetylate the kinase TBK1 for activation of antiviral innate immunity" 17 : 806-815, 2016

213 Li, S., "Mapping a dynamic innate immunity protein interaction network regulating type I interferon production" 35 : 426-440, 2011

214 Chen, L. T., "MSX1 modulates RLR-mediated innate antiviral signaling by facilitating assembly of TBK1-associated complexes" 197 : 199-207, 2016

215 Ng, M. H., "MIP-T3 is a negative regulator of innate type I IFN response" 187 : 6473-6482, 2011

216 Castanier, C., "MAVS ubiquitination by the E3 ligase TRIM25 and degradation by the proteasome is involved in type I interferon production after activation of the antiviral RIG-I-like receptors" 10 : 44-, 2012

217 Liu, S., "MAVS recruits multiple ubiquitin E3 ligases to activate antiviral signaling cascades" 2 : e00785-, 2013

218 Nandi, S., "MAVS protein is attenuated by rotavirus nonstructural protein 1" 9 : e92126-, 2014

219 Hou, F., "MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response" 146 : 448-461, 2011

220 James, S. J., "MAPK phosphatase 5 expression induced by influenza and other RNA virus infection negatively regulates IRF3 activation and type I interferon response" 10 : 1722-1734, 2015

221 Seo, M., "MAP4-regulated dynein-dependent trafficking of BTN3A1 controls the TBK1-IRF3 signaling axis" 113 : 14390-14395, 2016

222 Choudhary, C., "Lysine acetylation targets protein complexes and coregulates major cellular functions" 325 : 834-840, 2009

223 Belgnaoui, S. M., "Linear ubiquitination of NEMO negatively regulates the interferon antiviral response through disruption of the MAVS-TRAF3 complex" 12 : 211-222, 2012

224 Liu, S., "Lck/Hck/Fgr-mediated tyrosine phosphorylation negatively regulates TBK1 to restrain innate antiviral responses" 21 : 754-768, 2017

225 Zhang, W., "Lactate is a natural suppressor of RLR signaling by targeting MAVS" 178 : 176-189, 2019

226 Lubyova, B., "Kaposi’s sarcomaassociated herpesvirus-encoded vIRF-3 stimulates the transcriptional activity of cellular IRF-3 and IRF-7" 279 : 7643-7654, 2004

227 Hwang, S. W., "KSHV-encoded viral interferon regulatory factor 4(vIRF4)interacts with IRF7 and inhibits interferon alpha production" 486 : 700-705, 2017

228 Chen, W., "Jr Structural insights into interferon regulatory factor activation" 22 : 883-887, 2010

229 Chang, R. Y., "Japanese encephalitis virus non-coding RNA inhibits activation of interferon by blocking nuclear translocation of interferon regulatory factor 3" 166 : 11-21, 2013

230 Ye, J., "Japanese encephalitis virus NS5 inhibits type I interferon(IFN)production by blocking the nuclear translocation of IFN regulatory factor 3 and NFκB" 91 : e00039-17, 2017

231 Hyun-Cheol Lee, "Intracellular sensing of viral genomes and viral evasion" 생화학분자생물학회 51 : 1-13, 2019

232 Zhao, K., "Intracellular osteopontin stabilizes TRAF3 to positively regulate innate antiviral response" 6 : 23771-, 2016

233 Zhou, Y., "Interferon-inducible cytoplasmic lncLrrc55-AS promotes antiviral innate responses by strengthening IRF3 phosphorylation" 29 : 641-654, 2019

234 Huye, L. E., "Interferon regulatory factor 7 is activated by a viral oncoprotein through RIP-dependent ubiquitination" 27 : 2910-2918, 2007

235 Takeuchi, O., "Innate immunity to virus infection" 227 : 75-86, 2009

236 Joo, C. H., "Inhibition of interferon regulatory factor 7(IRF7)-mediated interferon signal transduction by the Kaposi’s sarcoma-associated herpesvirus viral IRF homolog vIRF3" 81 : 8282-8292, 2007

237 Irie, T., "Inhibition of interferon regulatory factor 3 activation by paramyxovirus V protein" 86 : 7136-7145, 2012

238 Randall, C. M., "Inhibition of interferon gene activation by death-effector domain-containing proteins from the molluscum contagiosum virus" 111 : E265-E272, 2014

239 Xu, L., "Inhibition of RIG-I and MDA5-dependent antiviral response by gC1qR at mitochondria" 106 : 1530-1535, 2009

240 Gao, L., "Inhibition of DNA-sensing pathway by Marek’s disease virus VP23protein through suppression of interferon regulatory factor 7 activation" 93 : e01934-18, 2019

241 Wei, F., "Induction of PGRN by influenza virus inhibits the antiviral immune responses through downregulation of type I interferons signaling" 15 : e1008062-, 2019

242 Liuyu, T., "Induction of OTUD4 by viral infection promotes antiviral responses through deubiquitinating and stabilizing MAVS" 29 : 67-79, 2019

243 Zhang, L., "Induction of OTUD1 by RNA viruses potently inhibits innate immune responses by promoting degradation of the MAVS/TRAF3/TRAF6 signalosome" 14 : e1007067-, 2018

244 Lu, B., "Induction of INKIT by viral infection negatively regulates antiviral responses through inhibiting phosphorylation of p65 and IRF3" 22 : 86-98, 2017

245 Wan, Y., "Inducible Rubicon facilitates viral replication by antagonizing interferon production" 14 : 607-620, 2017

246 Xu, G., "Inducible LGALS3BP/90K activates antiviral innate immune responses by targeting TRAF6 and TRAF3 complex" 15 : e1008002-, 2019

247 Barrat, F. J., "Importance of nucleic acid recognition in inflammation and autoimmunity" 67 : 323-336, 2016

248 Loo, Y. M., "Immune signaling by RIG-I-like receptors" 34 : 680-692, 2011

249 Kirchhoff, F., "Immune evasion and counteraction of restriction factors by HIV-1and other primate lentiviruses" 8 : 55-67, 2010

250 Servant, M. J., "Identification of the minimal phosphoacceptor site required for in vivo activation of interferon regulatory factor 3 in response to virus and double-stranded RNA" 278 : 9441-9447, 2003

251 Xing, J., "Identification of a role for TRIM29 in the control of innate immunity in the respiratory tract" 17 : 1373-1380, 2016

252 Seth, R. B., "Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3" 122 : 669-682, 2005

253 Li, Y., "ISG56 is a negative-feedback regulator of virus-triggered signaling and cellular antiviral response" 106 : 7945-7950, 2009

254 Honda, K., "IRFs : master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors" 6 : 644-658, 2006

255 Wang, J., "IRF1 promotes the innate immune response to viral infection by enhancing the activation of IRF3" 94 : e01231-20, 2020

256 Honda, K., "IRF-7 is the master regulator of type-I interferon-dependent immune responses" 434 : 772-777, 2005

257 Kawai, T., "IPS-1, an adaptor triggering RIG-I-and Mda5-mediated type I interferon induction" 6 : 981-988, 2005

258 Fitzgerald, K. A., "IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway" 4 : 491-496, 2003

259 Liu, X. Y., "IFN-induced TPR protein IFIT3potentiates antiviral signaling by bridging MAVS and TBK1" 187 : 2559-2568, 2011

260 Jiang, L. Q., "IFITM3 inhibits virus-triggered induction of type I interferon by mediating autophagosome-dependent degradation of IRF3" 15 : 858-867, 2018

261 Li, L., "Hydrolysis of 2'3’-cGAMP by ENPP1 and design of nonhydrolyzable analogs" 10 : 1043-1048, 2014

262 Lifland, A. W., "Human respiratory syncytial virus nucleoprotein and inclusion bodies antagonize the innate immune response mediated by MDA5 and MAVS" 86 : 8245-8258, 2012

263 Karim, R., "Human papillomavirus(HPV)upregulates the cellular deubiquitinase UCHL1 to suppress the keratinocyte’s innate immune response" 9 : e1003384-, 2013

264 Fu, Y. Z., "Human cytomegalovirus tegument protein UL82 inhibits STINGmediated signaling to evade antiviral immunity" 21 : 231-243, 2017

265 Fu, Y. Z., "Human cytomegalovirus protein UL42 antagonizes cGAS/MITAmediated innate antiviral response" 15 : e1007691-, 2019

266 이준규, "Human cytomegalovirus IE86 protein aa 136–289 mediates STING degradation and blocks the cGAS-STING pathway" 한국미생물학회 58 (58): 54-60, 2020

267 Kim, J. E., "Human cytomegalovirus IE2 86 kDa protein induces STING degradation and inhibits cGAMP-mediated IFN-β induction" 8 : 1854-, 2017

268 Jostins, L., "Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease" 491 : 119-124, 2012

269 Yang, Q., "Host HDAC4 regulates the antiviral response by inhibiting the phosphorylation of IRF3" 11 : 158-169, 2019

270 Tang, J. L., "Histone deacetylase 3 promotes innate antiviral immunity through deacetylation of TBK1" 12 : 261-278, 2020

271 Pan, S., "Herpes simplex virus 1 γ(1)34.5 protein inhibits STING activation that restricts viral replication" 92 : e01015–18-, 2018

272 Wang, S., "Herpes simplex virus 1 ubiquitin-specific protease UL36 inhibits beta interferon production by deubiquitinating TRAF3" 87 : 11851-11860, 2013

273 Zhang, D., "Herpes simplex virus 1 serine protease VP24 blocks the DNA-sensing signal pathway by abrogating activation of interferon regulatory factor 3" 90 : 5824-5829, 2016

274 Liu, X., "Herpes simplex virus 1 Inhibits TANK-binding kinase 1 through formation of the Us11-Hsp90 complex" 92 : e00402-18, 2018

275 Li, X. D., "Hepatitis C virus protease NS3/4A cleaves mitochondrial antiviral signaling protein off the mitochondria to evade innate immunity" 102 : 17717-17722, 2005

276 Raychoudhuri, A., "Hepatitis C virus infection impairs IRF-7 translocation and Alpha interferon synthesis in immortalized human hepatocytes" 84 : 10991-10998, 2010

277 Yi, G., "Hepatitis C virus NS4B can suppress STING accumulation to evade innate immune responses" 90 : 254-265, 2016

278 Kaukinen, P., "Hepatitis C virus NS2 protease inhibits host cell antiviral response by inhibiting IKKε and TBK1 functions" 85 : 71-82, 2013

279 Khan, M., "Hepatitis B virus-induced parkindependent recruitment of linear ubiquitin assembly complex (LUBAC) to mitochondria and attenuation of innate immunity" 12 : e1005693-, 2016

280 Liu, Y., "Hepatitis B virus polymerase disrupts K63-linked ubiquitination of STING to block innate cytosolic DNA-sensing pathways" 89 : 2287-2300, 2015

281 Wang, D., "Hepatitis A virus 3C protease cleaves NEMO to impair induction of beta interferon" 88 : 10252-10258, 2014

282 Ning, Y. J., "Heartland virus NSs protein disrupts host defenses by blocking the TBK1 kinase-IRF3 transcription factor interaction and signaling required for interferon induction" 292 : 16722-16733, 2017

283 Matthys, V. S., "Hantavirus GnT elements mediate TRAF3 binding and inhibit RIG-I/TBK1-directed beta interferon transcription by blocking IRF3 phosphorylation" 88 : 2246-2259, 2014

284 Wang, J., "HTLV-1 Tax impairs K63-linked ubiquitination of STING to evade host innate immunity" 232 : 13-21, 2017

285 Bodda, C., "HSV1 VP1-2 deubiquitinates STING to block type I interferon expression and promote brain infection" 217 : e20191422-, 2020

286 Christensen, M. H., "HSV-1 ICP27 targets the TBK1-activated STING signalsome to inhibit virus-induced type I IFN expression" 35 : 1385-1399, 2016

287 Lin, L., "HSPD1 interacts with IRF3 to facilitate interferon-beta induction" 9 : e114874-, 2014

288 Peng, Y., "HSCARG negatively regulates the cellular antiviral RIG-I like receptor signaling pathway by inhibiting TRAF3 ubiquitination via recruiting OTUB1" 10 : e1004041-, 2014

289 Lei, C. Q., "Glycogen synthase kinase 3β regulates IRF3 transcription factormediated antiviral response via activation of the kinase TBK1" 33 : 878-889, 2010

290 Rieder, M., "Genetic dissection of interferon-antagonistic functions of rabies virus phosphoprotein : inhibition of interferon regulatory factor 3 activation is important for pathogenicity" 85 : 842-852, 2011

291 Nie, Y., "GPATCH3 negatively regulates RLR-mediated innate antiviral responses by disrupting the assembly of VISA signalosome" 13 : e1006328-, 2017

292 Zhang, X., "GP73 represses host innate immune response to promote virus replication by facilitating MAVS and TRAF6 degradation" 13 : e1006321-, 2017

293 Rao, Y., "GCRV hijacks TBK1 to evade IRF7-mediated antiviral immune responses in grass carp Ctenopharyngodon idella" 93 : 492-499, 2019

294 Chen, Y., "Functional motifs responsible for human metapneumovirus M2-2-mediated innate immune evasion" 499 : 361-368, 2016

295 Di Sabatino, A., "Functional modulation of Crohn’s disease myofibroblasts by anti-tumor necrosis factor antibodies" 133 : 137-149, 2007

296 Ekanayaka, P., "Foot-and-mouth disease virus VP1 target the MAVS to inhibit type-I interferon signaling and VP1 E83K mutation results in virus attenuation" 16 : e1009057-, 2020

297 Wang, D., "Foot-and-mouth disease virus 3C protease cleaves NEMO to impair innate immune signaling" 86 : 9311-9322, 2012

298 Bozym, R. A., "Focal adhesion kinase is a component of antiviral RIG-I-like receptor signaling" 11 : 153-166, 2012

299 Kang, H., "Feline panleucopenia virus NS2 suppresses the host IFN-β induction by disrupting the interaction between TBK1 and STING" 9 : 23-, 2017

300 Chen, S., "Feline infectious peritonitis virus Nsp5 inhibits type I interferon production by cleaving NEMO at multiple sites" 12 : 43-, 2019

301 Matsumura, T., "Fascin1 suppresses RIG-I-like receptor signaling and interferon-β production by associating with IκB kinase ϵ(IKKϵ)in colon cancer" 293 : 6326-6336, 2018

302 Cai, B., "FOSL1 inhibits Type I interferon responses to malaria and viral infections by blocking TBK1 and TRAF3/TRIF interactions" 8 : e02161–16-, 2017

303 Xia, H., "Evasion of type I interferon by SARS-CoV-2" 33 : 108234-, 2020

304 Deschamps, T., "Evasion of the STING DNA-sensing pathway by VP11/12 of herpes simplex virus 1" 91 : e00535–17-, 2017

305 Wu, X., "Evasion of antiviral immunity through sequestering of TBK1/IKKε/IRF3 into viral inclusion bodies" 88 : 3067-3076, 2014

306 Wang, C., "Estrogen receptor alpha inhibits RLR-mediated immune response via ubiquitinating TRAF3" 27 : 1977-1983, 2015

307 Kang, J., "Enterovirus D68 protease 2A(pro)targets TRAF3 to subvert host innate immune responses" 95 : e01856-20, 2021

308 Wang, B., "Enterovirus 71 protease 2Apro targets MAVS to inhibit anti-viral type I interferon responses" 9 : e1003231-, 2013

309 Feng, Q., "Enterovirus 2Apro targets MDA5 and MAVS in infected cells" 88 : 3369-3378, 2014

310 Prins, K. C., "Ebola virus protein VP35 impairs the function of interferon regulatory factor-activating kinases IKKepsilon and TBK-1" 83 : 3069-3077, 2009

311 Chang, T. H., "Ebola Zaire virus blocks type I interferon production by exploiting the host SUMO modification machinery" 5 : e1000493-, 2009

312 He, X., "ERRα negatively regulates type I interferon induction by inhibiting TBK1-IRF3 interaction" 13 : e1006347-, 2017

313 Song, G., "E3 ubiquitin ligase RNF128 promotes innate antiviral immunity through K63-linked ubiquitination of TBK1" 17 : 1342-1351, 2016

314 Guo, Y., "E3 ubiquitin ligase ASB8 negatively regulates interferon via regulating TBK1/IKKi homeostasis" 121 : 195-203, 2020

315 Yang, Y., "Disruption of innate immunity due to mitochondrial targeting of a picornaviral protease precursor" 104 : 7253-7258, 2007

316 Rezelj, V. V., "Differential antagonism of human innate immune responses by tick-borne phlebovirus nonstructural proteins" 2 : e00234-17, 2017

317 Panda, S., "Deubiquitinase MYSM1 regulates innate immunity through inactivation of TRAF3 and TRAF6 complexes" 43 : 647-659, 2015

318 Angleró-Rodríguez, Y. I., "Dengue virus subverts the interferon induction pathway via NS2B/3 protease-IκB kinase epsilon interaction" 21 : 29-38, 2014

319 Dalrymple, N. A., "Dengue virus NS proteins inhibit RIGI/MAVS signaling by blocking TBK1/IRF3 phosphorylation: dengue virus serotype 1 NS4A is a unique interferon-regulating virulence determinant" 6 : e00553-00515, 2015

320 An, T., "DYRK2 negatively regulates type I interferon induction by promoting TBK1 degradation via Ser527 phosphorylation" 11 : e1005179-, 2015

321 Kayagaki, N., "DUBA : a deubiquitinase that regulates type I interferon production" 318 : 1628-1632, 2007

322 Kim, S. S., "DOK3 is required for IFN-β production by enabling TRAF3/TBK1complex formation and IRF3 activation" 193 : 840-848, 2014

323 Li, D., "DDX56 inhibits type I interferon by disrupting assembly of IRF3-IPO5to inhibit IRF3 nucleus import" 133 : jcs230409-, 2019

324 Fu, S. Z., "DDX56 cooperates with FMDV 3A to enhance FMDV replication by inhibiting the phosphorylation of IRF3" 64 : 109393-, 2019

325 Gu, L., "DDX3 directly regulates TRAF3 ubiquitination and acts as a scaffold to co-ordinate assembly of signalling complexes downstream from MAVS" 474 : 571-587, 2017

326 Zhang, K., "DDX19 inhibits type I interferon production by disrupting TBK1-IKKε-IRF3 interactions and promoting TBK1 and IKKε degradation" 26 : 1258-1272, 2019

327 Liu, W., "Cyclophilin A-regulated ubiquitination is critical for RIG-I-mediated antiviral immune responses" 6 : e24425-, 2017

328 Gao, J., "Cyclic(di)nucleotides : the common language shared by microbe and host" 30 : 79-87, 2016

329 Konno, H., "Cyclic dinucleotides trigger ULK1(ATG1)phosphorylation of STING to prevent sustained innate immune signaling" 155 : 688-698, 2013

330 Gao, P., "Cyclic [G(2’, 5’)pA(3’, 5’)p] is the metazoan second messenger produced by DNA-activated cyclic GMP-AMP synthase" 153 : 1094-1107, 2013

331 Wu, J., "Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA" 339 : 826-830, 2013

332 Zhang, X., "Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING" 51 : 226-235, 2013

333 Kato, K., "Cyclic GMP-AMP as an endogenous second messenger in innate immune signaling by cytosolic DNA" 86 : 541-566, 2017

334 Shang, G., "Cryo-EM structures of STING reveal its mechanism of activation by cyclic GMP-AMP" 567 : 389-393, 2019

335 Yang, S., "Control of antiviral innate immune response by protein geranylgeranylation" 5 : eaav7999-, 2019

336 Verpooten, D., "Control of TANK-binding kinase 1-mediated signaling by the gamma(1)34.5 protein of herpes simplex virus 1" 284 : 1097-1105, 2009

337 Yamada, T., "Constitutive aryl hydrocarbon receptor signaling constrains type I interferon-mediated antiviral innate defense" 17 : 687-694, 2016

338 Bauhofer, O., "Classical swine fever virus Npro interacts with interferon regulatory factor 3 and induces its proteasomal degradation" 81 : 3087-3096, 2007

339 Fiebach, A. R., "Classical swine fever virus N(pro)limits type I interferon induction in plasmacytoid dendritic cells by interacting with interferon regulatory factor 7" 85 : 8002-8011, 2011

340 Meylan, E., "Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus" 437 : 1167-1172, 2005

341 Gao, P., "CSK promotes innate immune response to DNA virus by phosphorylating MITA" 526 : 199-205, 2020

342 Wu, Z., "Binding of the duck tembusu virus protease to STING is mediated by NS2B and is crucial for STING cleavage and for impaired induction of IFN-β" 203 : 3374-3385, 2019

343 Ran, Y., "Autoubiquitination of TRIM26 links TBK1 to NEMO in RLR-mediated innate antiviral immune response" 8 : 31-43, 2016

344 Saitoh, T., "Atg9a controls dsDNA-driven dynamic translocation of STING and the innate immune response" 106 : 20842-20846, 2009

345 Chen, J., "Arterivirus nsp4 antagonizes interferon beta production by proteolytically cleaving NEMO at multiple sites" 93 : e00385-19, 2019

346 Pythoud, C., "Arenavirus nucleoprotein targets interferon regulatory factoractivating kinase IKKε" 86 : 7728-7738, 2012

347 Uma, B., "Antibacterial effect of hexane extract of sea urchin, Temnopleurus alexandri(Bell, 1884)" 2 : 1677-1680, 2010

348 Chen, H., "An alternative splicing isoform of MITA antagonizes MITAmediated induction of type I IFNs" 192 : 1162-1170, 2014

349 Chung, J. Y., "All TRAFs are not created equal: common and distinct molecular mechanisms of TRAF-mediated signal transduction" 115 : 679-688, 2002

350 Bender, S., "Activation of type I and III interferon response by mitochondrial and peroxisomal MAVS and inhibition by hepatitis C virus" 11 : e1005264-, 2015

351 Mukai, K., "Activation of STING requires palmitoylation at the Golgi" 7 : 11932-, 2016

352 Sin, W. X., "Activation and regulation of interferon-βin immune responses" 53 : 25-40, 2012

353 Lei, X., "Activation and evasion of type I interferon responses by SARS-CoV-2" 11 : 3810-, 2020

354 Wang, S., "AGO2 negatively regulates type I interferon signaling pathway by competition binding IRF3 with CBP/p300" 7 : 195-, 2017

355 Peng, D., "A novel function of F-Box protein FBXO17 in negative regulation of type I IFN signaling by recruiting PP2A for IFN regulatory factor 3 deactivation" 198 : 808-819, 2017

356 Paz, S., "A functional C-terminal TRAF3-binding site in MAVS participates in positive and negative regulation of the IFN antiviral response" 21 : 895-910, 2011