TRIM35 mediates protection against influenza infection by activating TRAF3 and degrading viral PB2

doi:10.1007/s13238-020-00734-6

Protein Cell

2020, Vol. 11

Issue (12) : 894-914 https://doi.org/10.1007/s13238-020-00734-6

RESEARCH ARTICLE

TRIM35 mediates protection against influenza infection by activating TRAF3 and degrading viral PB2

Nan Sun, Li Jiang, Miaomiao Ye, Yihan Wang, Guangwen Wang, Xiaopeng Wan, Yuhui Zhao, Xia Wen, Libin Liang, Shujie Ma, Liling Liu, Zhigao Bu, Hualan Chen(

), Chengjun Li(

)

State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China

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Abstract

Tripartite motif (TRIM) family proteins are important effectors of innate immunity against viral infections. Here we identified TRIM35 as a regulator of TRAF3 activation. Deficiency in or inhibition of TRIM35 suppressed the production of type I interferon (IFN) in response to viral infection. Trim35-deficient mice were more susceptible to influenza A virus (IAV) infection than were wild-type mice. TRIM35 promoted the RIG-Imediated signaling by catalyzing Lys63-linked polyubiquitination of TRAF3 and the subsequent formation of a signaling complex with VISA and TBK1. IAV PB2 polymerase countered the innate antiviral immune response by impeding the Lys63-linked polyubiquitination and activation of TRAF3. TRIM35 mediated Lys48-linked polyubiquitination and proteasomal degradation of IAV PB2, thereby antagonizing its suppression of TRAF3 activation. Our in vitro and in vivo findings thus reveal novel roles of TRIM35, through catalyzing Lys63-or Lys48-linked polyubiquitination, in RIG-I antiviral immunity and mechanism of defense against IAV infection.

Keywords influenza A virus PB2 TRIM35 TRAF3 ubiquitination antiviral immunity

Corresponding Author(s): Hualan Chen,Chengjun Li

Online First Date: 14 September 2020 Issue Date: 22 December 2020

Cite this article:

Nan Sun,Li Jiang,Miaomiao Ye, et al. TRIM35 mediates protection against influenza infection by activating TRAF3 and degrading viral PB2[J]. Protein Cell, 2020, 11(12): 894-914.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-020-00734-6
https://academic.hep.com.cn/pac/EN/Y2020/V11/I12/894

1	R Arranz, R Coloma, FJ Chichon, JJ Conesa, JL Carrascosa, JM Valpuesta, J Ortin, J Martin-Benito (2012) The structure of native influenza virion ribonucleoproteins. Science 338:1634–1637 https://doi.org/10.1126/science.1228172
2	A Baum, R Sachidanandam, A Garcia-Sastre (2010) Preference of RIG-I for short viral RNA molecules in infected cells revealed by next-generation sequencing. Proc Natl Acad Sci USA 107:16303–16308 https://doi.org/10.1073/pnas.1005077107
3	Z Chen, Z Wang, W Guo, Z Zhang, F Zhao, Y Zhao, D Jia, J Ding, H Wang, M Yaoet al. (2015) TRIM35 Interacts with pyruvate kinase isoform M2 to suppress the Warburg effect and tumorigenicity in hepatocellular carcinoma. Oncogene 34:3946–3956 https://doi.org/10.1038/onc.2014.325
4	ME Davis, MU Gack (2015) Ubiquitination in the antiviral immune response. Virology 479–480:52–65 https://doi.org/10.1016/j.virol.2015.02.033
5	A Dias, D Bouvier, T Crepin, AA McCarthy, DJ Hart, F Baudin, S Cusack, RW Ruigrok (2009) The cap-snatching endonuclease of influenza virus polymerase resides in the PA subunit. Nature 458:914–918 https://doi.org/10.1038/nature07745
6	KA Fitzgerald, SM McWhirter, KL Faia, DC Rowe, E Latz, DT Golenbock, AJ Coyle, SM Liao, T Maniatis (2003) IKK epsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat Immunol 4:491–496 https://doi.org/10.1038/ni921
7	G Gabriel, B Dauber, T Wolff, O Planz, HD Klenk, J Stech (2005) The viral polymerase mediates adaptation of an avian influenza virus to a mammalian host. Proc Natl Acad Sci USA 102:18590–18595 https://doi.org/10.1073/pnas.0507415102
8	MU Gack, RA Albrecht, T Urano, KS Inn, IC Huang, E Carnero, M Farzan, S Inoue, JU Jung, A Garcia-Sastre (2009) Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I. Cell Host Microbe 5:439–449 https://doi.org/10.1016/j.chom.2009.04.006
9	KM Graef, FT Vreede, YF Lau, AW McCall, SM Carr, K Subbarao, E Fodor (2010) The PB2 subunit of the influenza virus RNA polymerase affects virulence by interacting with the mitochondrial antiviral signaling protein and inhibiting expression of beta interferon. J Virol 84:8433–8445 https://doi.org/10.1128/JVI.00879-10
10	H Hacker, PH Tseng, M Karin (2011) Expanding TRAF function: TRAF3 as a tri-faced immune regulator. Nat Rev Immunol 11:457–468 https://doi.org/10.1038/nri2998
11	S Hatakeyama (2017) TRIM family proteins: roles in autophagy, immunity, and carcinogenesis. Trends Biochem Sci 42:297–311 https://doi.org/10.1016/j.tibs.2017.01.002
12	M Hatta, P Gao, P Halfmann, Y Kawaoka (2001) Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science 293:1840–1842 https://doi.org/10.1126/science.1062882
13	A Iwai, T Shiozaki, T Kawai, S Akira, Y Kawaoka, A Takada, H Kida, T Miyazaki (2010) Influenza A virus polymerase inhibits type I interferon induction by binding to interferon beta promoter stimulator 1. J Biol Chem 285:32064–32074 https://doi.org/10.1074/jbc.M110.112458
14	P Jiao, G Tian, Y Li, G Deng, Y Jiang, C Liu, W Liu, Z Bu, Y Kawaoka, H Chen (2008) A single-amino-acid substitution in the NS1 protein changes the pathogenicity of H5N1 avian influenza viruses in mice. J Virol 82:1146–1154 https://doi.org/10.1128/JVI.01698-07
15	CAP Joazeiro, AM Weissman (2000) RING finger proteins: mediators of ubiquitin ligase activity. Cell 102:549–552 https://doi.org/10.1016/S0092-8674(00)00077-5
16	T Kawai, S Akira (2006) Innate immune recognition of viral infection. Nat Immunol 7:131–137 https://doi.org/10.1038/ni1303
17	T Kawai, K Takahashi, S Sato, C Coban, H Kumar, H Kato, KJ Ishii, O Takeuchi, S Akira (2005) IPS-1, an adaptor triggering RIG-Iand Mda5-mediated type I interferon induction. Nat Immunol 6:981–988 https://doi.org/10.1038/ni1243
18	F Kimura, S Suzu, Y Nakamura, Y Nakata, M Yamada, N Kuwada, T Matsumura, T Yamashita, T Ikeda, K Satoet al. (2003) Cloning and characterization of a novel RING-B-box-coiled-coil protein with apoptotic function. J Biol Chem 278:25046–25054 https://doi.org/10.1074/jbc.M303438200
19	E Kowalinski, T Lunardi, AA McCarthy, J Louber, J Brunel, B Grigorov, D Gerlier, S Cusack (2011) Structural basis for the activation of innate immune pattern-recognition receptor RIG-I by viral RNA. Cell 147:423–435 https://doi.org/10.1016/j.cell.2011.09.039
20	Z Li, H Chen, P Jiao, G Deng, G Tian, Y Li, E Hoffmann, RG Webster, Y Matsuoka, K Yu (2005) Molecular basis of replication of duck H5N1 influenza viruses in a mammalian mouse model. J Virol 79:12058–12064 https://doi.org/10.1128/JVI.79.18.12058-12064.2005
21	Z Li, Y Jiang, P Jiao, A Wang, F Zhao, G Tian, X Wang, K Yu, Z Bu, H Chen (2006) The NS1 gene contributes to the virulence of H5N1 avian influenza viruses. J Virol 80:11115–11123 https://doi.org/10.1128/JVI.00993-06
22	Y Li, H Wu, W Wu, W Zhuo, WX Liu, YX Zhang, MZ Cheng, YG Chen, N Gao, HT Yuet al. (2014) Structural insights into the TRIM family of ubiquitin E3 ligases. Cell Res 24:762–765 https://doi.org/10.1038/cr.2014.46
23	LB Liang, L Jiang, JP Li, QQ Zhao, JG Wang, XJ He, SY Huang, Q Wang, YH Zhao, GW Wanget al. (2019) Low polymerase activity attributed to PA drives the acquisition of the PB2 E627K mutation of H7N9 avian influenza virus in mammals. mBio 10: e01162–19 https://doi.org/10.1128/mBio.01162-19
24	S Liedmann, ER Hrincius, C Guy, D Anhlan, R Dierkes, R Carter, G Wu, P Staeheli, DR Green, T Wolffet al. (2014) Viral suppressors of the RIG-I-mediated interferon response are prepackaged in influenza virions. Nat Commun 5:5645 https://doi.org/10.1038/ncomms6645
25	YM Loo, M Gale (2011) Immune signaling by RIG-I-like receptors. Immunity 34:680–692 https://doi.org/10.1016/j.immuni.2011.05.003
26	WY Luo, J Zhang, LB Liang, GW Wang, QB Li, PY Zhu, Y Zhou, JP Li, YH Zhao, N Sunet al. (2018) Phospholipid scramblase 1 interacts with influenza A virus NP, impairing its nuclear import and thereby suppressing virus replication. PLoS Pathog 14:e1006851 https://doi.org/10.1371/journal.ppat.1006851
27	AP Mao, S Li, B Zhong, Y Li, J Yan, Q Li, C Teng, HB Shu (2010) Virus-triggered ubiquitination of TRAF3/6 by cIAP1/2 is essential for induction of interferon-beta (IFN-beta) and cellular antiviral response. J Biol Chem 285:9470–9476 https://doi.org/10.1074/jbc.M109.071043
28	E Meylan, J Curran, K Hofmann, D Moradpour, M Binder, R Bartenschlager, R Tschopp (2005) Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature 437:1167–1172 https://doi.org/10.1038/nature04193
29	M Mibayashi, L Martinez-Sobrido, YM Loo, WB Cardenas, M Jr Gale, A Garcia-Sastre (2007) Inhibition of retinoic acid-inducible gene I-mediated induction of beta interferon by the NS1 protein of influenza A virus. J Virol 81:514–524 https://doi.org/10.1128/JVI.01265-06
30	JY Min, C Santos, A Fitch, A Twaddle, Y Toyoda, JV DePasse, E Ghedin, K Subbarao (2013) Mammalian adaptation in the PB2 gene of Avian H5N1 influenza virus. J Virol 87:10884–10888 https://doi.org/10.1128/JVI.01016-13
31	A Moeller, RN Kirchdoerfer, CS Potter, B Carragher, IA Wilson (2012) Organization of the influenza virus replication machinery. Science 338:1631–1634 https://doi.org/10.1126/science.1227270
32	J Mukaigawa, DP Nayak (1991) Two signals mediate nuclear localization of influenza virus (A/WSN/33) polymerase basic protein 2. J Virol 65:245–253 https://doi.org/10.1128/JVI.65.1.245-253.1991
33	K Ozato, DM Shin, TH Chang, HC Morse (2008) TRIM family proteins and their emerging roles in innate immunity. Nat Rev Immunol 8:849–860 https://doi.org/10.1038/nri2413
34	CM Pickart, D Fushman (2004) Polyubiquitin chains: polymeric protein signals. Curr Opin Chem Biol 8:610–616 https://doi.org/10.1016/j.cbpa.2004.09.009
35	SJ Plotch, M Bouloy, I Ulmanen, RM Krug (1981) A unique cap(m7G pppXm)-dependent influenza virion endonuclease cleaves capped RNAs to generate the primers that initiate viral RNA transcription. Cell 23:847–858 https://doi.org/10.1016/0092-8674(81)90449-9
36	W Qian, X Wei, K Guo, Y Li, X Lin, Z Zou, H Zhou, M Jin (2017) The C-terminal effector domain of non-structural protein 1 of influenza A virus blocks IFN-β production by targeting TNF receptorassociated factor 3. Front Immunol 8:779 https://doi.org/10.3389/fimmu.2017.00779
37	R Rajsbaum, A Garcia-Sastre, GA Versteeg (2014) TRIMmunity: the roles of the TRIM E3-ubiquitin ligase family in innate antiviral immunity. J Mol Biol 426:1265–1284 https://doi.org/10.1016/j.jmb.2013.12.005
38	E Rieser, SM Cordier, H Walczak (2013) Linear ubiquitination: a newly discovered regulator of cell signalling. Trends Biochem Sci 38:94–102 https://doi.org/10.1016/j.tibs.2012.11.007
39	M Sadowski, B Sarcevic (2010) Mechanisms of mono- and polyubiquitination: Ubiquitination specificity depends on compatibility between the E2 catalytic core and amino acid residues proximal to the lysine. Cell Div 5:19 https://doi.org/10.1186/1747-1028-5-19
40	SK Saha, EM Pietras, JQ He, JR Kang, SY Liu, G Oganesyan, A Shahangian, B Zarnegar, TL Shiba, Y Wanget al. (2006) Regulation of antiviral responses by a direct and specific interaction between TRAF3 and Cardif. EMBO J 25:3257–3263 https://doi.org/10.1038/sj.emboj.7601220
41	RB Seth, LJ Sun, CK Ea, ZJ Chen (2005) Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappa B and IRF3. Cell 122:669–682 https://doi.org/10.1016/j.cell.2005.08.012
42	EK Subbarao, W London, BR Murphy (1993) A single amino acid in the PB2 gene of influenza A virus is a determinant of host range. J Virol 67:1761–1764 https://doi.org/10.1128/JVI.67.4.1761-1764.1993
43	MR Thompson, JJ Kaminski, EA Kurt-Jones, KA Fitzgerald (2011) Pattern recognition receptors and the innate immune response to viral infection. Viruses 3:920–940 https://doi.org/10.3390/v3060920
44	PH Tseng, A Matsuzawa, W Zhang, T Mino, DA Vignali, M Karin (2010) Different modes of ubiquitination of the adaptor TRAF3 selectively activate the expression of type I interferons and proinflammatory cytokines. Nat Immunol 11:70–75 https://doi.org/10.1038/ni.1819
45	M van Gent, KMJ Sparrer, MU Gack (2018) TRIM proteins and their roles in antiviral host defenses. Annu Rev Virol 5:385–405 https://doi.org/10.1146/annurev-virology-092917-043323
46	ZT Varga, I Ramos, R Hai, M Schmolke, A Garcia-Sastre, A Fernandez-Sesma, P Palese (2011) The influenza virus protein PB1-F2 inhibits the induction of type I interferon at the level of the MAVS adaptor protein. PLoS Pathog 7:e1002067 https://doi.org/10.1371/journal.ppat.1002067
47	Y Wang, I Shaked, SM Stanford, W Zhou, JM Curtsinger, Z Mikulski, ZR Shaheen, G Cheng, K Sawatzke, AM Campbellet al. (2013) The autoimmunity-associated gene PTPN22 potentiates toll-like receptor-driven, type 1 interferon-dependent immunity. Immunity 39:111–122 https://doi.org/10.1016/j.immuni.2013.06.013
48	Y Wang, S Yan, B Yang, Y Wang, H Zhou, Q Lian, B Sun (2015) TRIM35 negatively regulates TLR7- and TLR9-mediated type I interferon production by targeting IRF7. FEBS Lett 589:1322–1330 https://doi.org/10.1016/j.febslet.2015.04.019
49	M Weber, A Gawanbacht, M Habjan, A Rang, C Bomer, AM Schmidt, S Veitinger, R Jacob, S Devignot, G Kochset al. (2013) Incoming RNA virus nucleocapsids containing a 5′-triphosphorylated genome activate RIG-I and antiviral signaling. Cell Host Microbe 13:336–346 https://doi.org/10.1016/j.chom.2013.01.012
50	LG Xu, YY Wang, KJ Han, LY Li, ZH Zhai, HB Shu (2005) VISA is an adapter protein required for virus-triggered IFN-beta signaling. Mol Cell 19:727–740 https://doi.org/10.1016/j.molcel.2005.08.014
51	S Yamayoshi, M Watanabe, H Goto, Y Kawaoka (2016) Identification of a novel viral protein expressed from the PB2 segment of influenza A virus. J Virol 90:444–456 https://doi.org/10.1128/JVI.02175-15
52	C Yi, Z Zhao, S Wang, X Sun, D Zhang, X Sun, A Zhang, M Jin (2017) Influenza A virus PA antagonizes interferon-beta by interacting with interferon regulatory factor 3. Front Immunol 8:1051 https://doi.org/10.3389/fimmu.2017.01051
53	M Yoneyama, K Onomoto, M Jogi, T Akaboshi, T Fujita (2015) Viral RNA detection by RIG-I-like receptors. Curr Opin Immunol 32:48–53 https://doi.org/10.1016/j.coi.2014.12.012
54	P Yuan, M Bartlam, Z Lou, S Chen, J Zhou, X He, Z Lv, R Ge, X Li, T Denget al. (2009) Crystal structure of an avian influenza polymerase PA(N) reveals an endonuclease active site. Nature 458:909–913 https://doi.org/10.1038/nature07720
55	T Zhang, Z Ye, X Yang, Y Qin, Y Hu, X Tong, W Lai, X Ye (2017) NEDDylation of PB2 reduces its stability and blocks the replication of influenza A virus. Sci Rep 7:43691 https://doi.org/10.1038/srep43691
56	Q Zhu, H Yang, W Chen, W Cao, G Zhong, P Jiao, G Deng, K Yu, C Yanget al. (2008) A naturally occurring deletion in its NS gene contributes to the attenuation of an H5N1 swine influenza virus in chickens. J Virol 82:220–228 https://doi.org/10.1128/JVI.00978-07
57	K Zhu, X Wang, LG Ju, Y Zhu, J Yao, Y Wang, M Wu, LY Li (2015) WDR82 negatively regulates cellular antiviral response by mediating TRAF3 polyubiquitination in multiple cell lines. J Immunol 195:5358–5366 https://doi.org/10.4049/jimmunol.1500339
58	PY Zhu, LB Liang, XY Shao, WY Luo, ST Jiang, QQ Zhao, N Sun, YH Zhao, JP Li, JG Wanget al. (2017) Host cellular protein TRAPPC6A delta interacts with influenza A virus M2 protein and regulates viral propagation by modulating M2 trafficking. J Virol 91:e01757-16 https://doi.org/10.1128/JVI.01757-16

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