口蹄疫病毒3D蛋白促进TLR3介导的Ⅰ型干扰素产生

doi:10.11843/j.issn.0366-6964.2020.08.016

Abstract

Abstract: Foot-and-mouth disease (FMD) caused by FMD virus (FMDV) is an acute, hot and highly contagious disease. FMDV causes a series of severe inflammatory response, and TLR3 pathway is one of the major cellular inflammatory. In order to study the effect of FMDV protein on TLR3 pathway, we screened the FMDV proteins affecting on TLR3 pathway by reporter assays. Then candidate protein effect on transcription of TLR3 pathway downstream genes was verified by Q-PCR assay. TLR3 signaling pathway proteins interacted with candidate protein was further verified by co-immunocoprecipitation. Finally, we detected phosphorylation level of TLR3 pathway downstream proteins in candidate protein-overexpressed 293-TLR3 cells by Western blot. The luciferase assays and Q-PCR results showed that FMDV 3D potentiated poly (I:C)-triggered TLR3 signaling pathway and transcription of TLR3 pathway downstream genes, respectively. In addition, co-immunocoprecipitation showed that FMDV 3D interacted with TLR3. Furthermore, FMDV 3D increased the phosphorylation level of TLR3 pathway downstream protein. In conclusion, FMDV 3D potentiated type Ⅰ interferon mediated by TLR3 pathway, which regulate innate immune response.

Key words: FMDV, innate immune, TLR3, 3D protein

CLC Number:

S852.659.6

LI Lulu, ZHANG Jing, LI Dan, ZHENG Haixue. Foot-and-Mouth Disease Virus 3D Protein Positively Regulates the Production of InterferonⅠMediated by TLR3[J]. Acta Veterinaria et Zootechnica Sinica, 2020, 51(8): 1923-1931.

References 41

[1]	AKIRA S, UEMATSU S, TAKEUCHI O. Pathogen recognition and innate immunity[J]. Cell, 2006, 124(4):783-801.
[2]	CHEN G, SHAW M H, KIM Y G, et al. NOD-like receptors:role in innate immunity and inflammatory disease[J]. Annu Rev Pathol, 2009, 4:365-398.
[3]	JIN X H, ZHENG L L, SONG M R, et al. A nano silicon adjuvant enhances inactivated transmissible gastroenteritis vaccine through activation the Toll-like receptors and promotes humoral and cellular immune responses[J]. Nanomedicine, 2018, 14(4):1201-1212.
[4]	KUMAR H, KAWAI T, AKIRA S. Pathogen recognition in the innate immune response[J]. Biochem J, 2009, 420(1):1-16.
[5]	PILA E A, TARRABAIN M, KABORE A L, et al. A novel toll-like receptor (TLR) influences compatibility between the gastropod Biomphalaria glabrata, and the digenean trematode Schistosoma mansoni[J]. PLoS Pathog, 2016, 12(3):e1005513.
[6]	CAO Y, SUN Y, CHANG H Y, et al. The E3 ubiquitin ligase RNF 182 inhibits TLR-triggered cytokine production through promoting p65 ubiquitination and degradation[J]. FEBS Lett, 2019, 593(22):3210-3219.
[7]	SONG Y, LI P S, QIN L P, et al. CUL4B negatively regulates Toll-like receptor-triggered proinflammatory responses by repressing Pten transcription[J]. Cell Mol Immunol, 2019, doi:10. 1038/s41423-019-0323-0.
[8]	PARK A, RA E A, LEE T A, et al. HCMV-encoded US7 and US8 act as antagonists of innate immunity by distinctively targeting TLR-signaling pathways[J]. Nat Commun, 2019, 10:4670.
[9]	AKIRA S, TAKEDA K. Toll-like receptor signalling[J]. Nat Rev Immunol, 2004, 4(7):499-511.
[10]	BARBALAT R, EWALD S E, MOUCHESS M L, et al. Nucleic acid recognition by the innate immune system[J]. Annu Rev Immunol, 2011, 29:185-214.
[11]	BARTON G M, KAGAN J C. A cell biological view of Toll-like receptor function:regulation through compartmentalization[J]. Nat Rev Immunol, 2009, 9(8):535-542.
[12]	CHAI H C, CHUA K H, LIM S K, et al. Insight into gene polymorphisms involved in toll-like receptor/interferon signalling pathways for systemic lupus erythematosus in South East Asia[J]. J Immunol Res, 2014, 2014:529167.
[13]	DE BOUTEILLER O, MERCK E, HASAN U A, et al. Recognition of double-stranded RNA by human toll-like receptor 3 and downstream receptor signaling requires multimerization and an acidic pH[J]. J Biol Chem, 2005, 280(46):38133-38145.
[14]	KLEINMAN M E, YAMADA K, TAKEDA A, et al. Sequence-and target-independent angiogenesis suppression by siRNA via TLR3[J]. Nature, 2008, 452(7187):591-597.
[15]	SCHULZ O, DIEBOLD S S, CHEN M, et al. Toll-like receptor 3 promotes cross-priming to virus-infected cells[J]. Nature, 2005, 433(7028):887-892.
[16]	BARNETT P V, GEALE D W, CLARKE G, et al. A review of OIE country status recovery using vaccinate-to-live versus vaccinate-to-die foot-and-mouth disease response policies I:benefits of higher potency vaccines and associated NSP DIVA test systems in post-outbreak surveillance[J]. Transbound Emerg Dis, 2015, 62(4):367-387.
[17]	JAMAL S M, BELSHAM G J. Foot-and-mouth disease:past, present and future[J]. Vet Res, 2013, 44(1):116.
[18]	KNIGHT-JONES T J D, RUSHTON J. The economic impacts of foot and mouth disease-what are they, how big are they and where do they occur?[J]. Prev Vet Med, 2013, 112(3-4):161-173.
[19]	LI D, LEI C Q, XU Z S, et al. Foot-and-mouth disease virus non-structural protein 3A inhibits the interferon-β signaling pathway[J]. Sci Rep, 2016, 6:21888.
[20]	WANG D, FANG L R, LI K, et al. Foot-and-mouth disease virus 3C protease cleaves NEMO to impair innate immune signaling[J]. J Virol, 2012, 86(17):9311-9322.
[21]	LI D, YANG W P, YANG F, et al. The VP3 structural protein of foot-and-mouth disease virus inhibits the IFN-β signaling pathway[J]. FASEB J, 2016, 30(5):1757-1766.
[22]	LI M, XIN T, GAO X T, et al. Foot-and-mouth disease virus non-structural protein 2B negatively regulates the RLR-mediated IFN-β induction[J]. Biochem Biophys Res Commun, 2018, 504(1):238-244.
[23]	FENG H H, ZHU Z X, CAO W J, et al. Foot-and-mouth disease virus induces lysosomal degradation of NME1 to impair p53-regulated interferon-inducible antiviral genes expression[J]. Cell Death Dis, 2018, 9(9):885.
[24]	FU S Z, YANG W P, RU Y, et al. DDX56 cooperates with FMDV 3A to enhance FMDV replication by inhibiting the phosphorylation of IRF3[J]. Cell Signal, 2019, 64:109393.
[25]	何艳春, 杨文萍, 付绍祖, 等. PCBP2促进口蹄疫病毒增殖的机制研究[J]. 畜牧兽医学报, 2018, 49(7):1451-1459.HE Y C, YANG W P, FU S Z, et al. The research on molecular mechanism of PCBP2 promoting the multiplication of foot-and-mouth disease virus[J]. Acta Veterinaria et Zootechnica Sinica, 2018, 49(7):1451-1459. (in Chinese)
[26]	LI D, FU S Z, WU Z Q, et al. DDX56 inhibits type I interferon by disrupting assembly of IRF3-IPO5 to inhibit IRF3 nucleus import[J]. J Cell Sci, 2020, 133(5):jcs230409.
[27]	WANG J Y, ZENG Y, XU S, et al. A naturally occurring deletion in the effector domain of H5N1 swine influenza virus nonstructural protein 1 regulates viral fitness and host innate immunity[J]. J Virol, 2018, 92(11):e00149-18.
[28]	YANG W P, RU Y, REN J J, et al. G3BP1 inhibits RNA virus replication by positively regulating RIG-I-mediated cellular antiviral response[J]. Cell Death Dis, 2019, 10(12):946.
[29]	YE W, HU M M, LEI C Q, et al. TRIM8 negatively regulates TLR3/4-mediated innate immune response by blocking TRIF-TBK1 interaction[J]. J Immunol, 2017, 199(5):1856-1864.
[30]	付绍祖, 李露露, 张敬, 等. 猪源DDX56对口蹄疫病毒的复制及其对病毒诱导的RLR通路调节的研究[J]. 畜牧兽医学报, 2019, 50(9):1849-1856.FU S Z, LI L L, ZHANG J, et al. Porcine DDX56 regulates the foot and mouth disease virus replication and the virus-triggered RLR pathway[J]. Acta Veterinaria et Zootechnica Sinica, 2019, 50(9):1849-1856. (in Chinese)
[31]	LI D, YANG W P, REN J J, et al. The E3 ubiquitin ligase TBK1 mediates the degradation of multiple picornavirus VP3 proteins by phosphorylation and ubiquitination[J]. J Virol, 2019, 93(23):e01438-19.
[32]	DOMINGO E, BARANOWSKI E, ESCARMI S C, et al. Foot-and-mouth disease virus[J]. Comp Immunol Microbiol Infect Dis, 2002, 25(5-6):297-308.
[33]	杜平, 尚佑军, 贺延玉, 等. 口蹄疫病毒3D基因的克隆及其编码蛋白的结构和功能预测[J]. 甘肃农业大学学报, 2009, 44(2):20-25.DU P, SHANG Y J, HE Y Y, et al. Cloning of foot-and-mouth disease virus 3D gene and its structure and function[J]. Journal of Gansu Agricultural University, 2009, 44(2):20-25. (in Chinese)
[34]	XUE Q, LIU H S, ZENG Q Y, et al. The DEAD-box RNA helicase DDX1 interacts with the viral protein 3D and inhibits foot-and-mouth disease virus replication[J]. Virol Sin, 2019, 34(6):610-617.
[35]	鲁彬. 口蹄疫病毒3D基因的真核表达及其表达产物的功能分析[J]. 中国兽医科学, 2006, 36(10):800-804.LU B. Eukaryotic expression of foot-and-mouth disease virus 3D gene and functional analysis of the expressed product[J]. Veterinary Science in China, 2006, 36(10):800-804. (in Chinese)
[36]	GARCIÍA-BRIONES M M, BLANCO E, CHIVA C, et al. Immunogenicity and T cell recognition in swine of foot-and-mouth disease virus polymerase 3D[J]. Virology, 2004, 322(2):264-275.
[37]	SONG X Q, LIU S, WANG W D, et al. E3 ubiquitin ligase RNF170 inhibits innate immune responses by targeting and degrading TLR3 in murine cells[J]. Cell Mol Immunol, 2019, doi:10. 1038/s41423-019-0236-y.
[38]	ZHONG X, FENG L, XU W H, et al. The zinc-finger protein ZFYVE1 modulates TLR3-mediated signaling by facilitating TLR3 ligand binding[J]. Cell Mol Immunol, 2019.doi:10. 1038/s41423-019-0265-6.
[39]	ABUJAMRA A L, SPANJAARD R A, AKINSHEYE I, et al. Leukemia virus long terminal repeat activates NFκB pathway by a TLR3-dependent mechanism[J]. Virology, 2006, 345(2):390-403.
[40]	ALEXOPOULOU L, HOLT A C, MEDZHITOV R, et al. Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3[J]. Nature, 2001, 413(6857):732-738.
[41]	HUAI W W, SONG H, YU Z X, et al. Mint3 potentiates TLR3/4-and RIG-I-induced IFN-β expression and antiviral immune responses[J]. Proc Natl Acad Sci U S A, 2016, 113(42):11925-11930.

Foot-and-Mouth Disease Virus 3D Protein Positively Regulates the Production of InterferonⅠMediated by TLR3

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References 41

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	ZHU Jingjing, DAI Zhenglie, WANG Han, LI Xiangchen, ZHAO Ayong, ZHOU Xiaolong, YANG Songbai. Analysis of Differential Expression Profile of LncRNA in PK15 Cells Infected with Japanese Encephalitis Virus [J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(1): 272-281.
[2]	QIAN Man, LIAO Chengshui, ZHANG Chunjie. Research Progress on Extracellular Traps of Innate Immune Cells Stimulated by Foodborne Pathogens [J]. Acta Veterinaria et Zootechnica Sinica, 2021, 52(7): 1800-1808.
[3]	ZHANG Fanfan, ZENG Yanbing, FANG Shaopei, LI Haiqin, KANG Zhaofeng, TAN Meifang, TAN Jia, YANG Qun, WEI Qipeng. Research Progress in Duck Tembusu Virus Disease [J]. Acta Veterinaria et Zootechnica Sinica, 2021, 52(6): 1489-1497.
[4]	SHI Xijuan, LIU Yuanzi, ZHANG Dajun, HOU Jing, SHEN Chaochao, YANG Bo, ZHANG Ting, YUAN Xingguo, REN Ruirui, DU Xiaohua, ZHANG Keshan, ZHENG Haixue, LIU Xiangtao. Porcine Cathepsin S Inhibits the Replication of Foot-and-Mouth Disease Virus Serotype O in PK-15 Cells [J]. Acta Veterinaria et Zootechnica Sinica, 2021, 52(6): 1652-1661.
[5]	ZENG Zongbo, MA Xusheng, LUO Zhikuan, QI Yayin, ZHENG Haixue. Programmed Cell Death Factor 10 Inhibits Type Ⅰ Interferon Expression and Promotes the Replication of Foot-and-mouth Disease Virus [J]. Acta Veterinaria et Zootechnica Sinica, 2021, 52(2): 450-459.
[6]	LI Xian, ZHANG Zhongwang, ZHANG Fudong, Lü Jianliang, LI Jiahao, PAN Li. Evaluation of the Characteristics of Mannosylated Chitosan PLGA Nanospheres as a Delivery System for DNA Vaccine of A/FMDV [J]. Acta Veterinaria et Zootechnica Sinica, 2021, 52(12): 3557-3568.
[7]	LI Pengfei, GONG Zhenli, DU Xiaohua, JIANG Tao. Real-time Analysis of the Interaction between RGD Motif and Integrin Based on Surface Plasmon Resonance (SPR) [J]. Acta Veterinaria et Zootechnica Sinica, 2021, 52(1): 256-261.
[8]	ZHAO Xueliang, LIU Haijin, XIAO Sa, WANG Xinglong, YANG Zengqi. Long Non-coding RNAs: Novel Regulators of Virus-host Interactions [J]. Acta Veterinaria et Zootechnica Sinica, 2020, 51(9): 2059-2067.
[9]	FU Shaozu, LI Lulu, ZHANG Jing, LI Dan, ZHENG Haixue. Porcine DDX56 Regulates the Foot and Mouth Disease Virus Replication and the Virus-triggered RLR Pathway [J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2019, 50(9): 1849-1856.
[10]	TANG Zequn, LUO Haiyan, GE Ming, GUO Rong, XU Danlei, ZHANG Ruili. Preparation of Monoclonal Antibody against chTLR3 and Its Preliminary Application [J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2019, 50(6): 1292-1300.
[11]	LUO Yu, XU Jia, ZHANG Chaoying, JIANG Chunyan, HE Haijian, YU Jianguo, ZHANG Hongbing. The Expression and Functional Analysis of IL-17 Cytokine Family in Enterotoxigenic E.coli Infected IPEC-J2 Cells [J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2019, 50(4): 830-839.
[12]	HE Yan-chun, YANG Wen-ping, FU Shao-zu, ZHENG Hai-xue, YANG Xiao-pu. The Research on Molecular Mechanism of PCBP2 Promoting the Multiplication of Foot-and-mouth Disease Virus [J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2018, 49(7): 1451-1459.
[13]	WEI Nan-nan, XU Shou-xing, SHI Xi-juan, LU Bing-zhou, ZHANG Ke-shan, ZHENG Hai-xue, LIU Xiang-tao. TPL2 Enhances the Replication of Foot-and-mouth Disease Virus in BHK-21 Cells [J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2018, 49(6): 1204-1211.
[14]	BA Xue-li, ZHANG Ai-lian, HUANG Jiong, CAO Hui, ZHAO Bing, WANG Dan-yang. Adjuvant Effect of Xinjiang Wild Cistanche deserticola Y.C.Ma Crude Polysaccharides on Foot-and-mouth Disease Vaccines in Mice [J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2017, 48(8): 1535-1542.
[15]	LI Hong-jie, WANG Xiao-xue, GAO Dong-sheng, HUANG Hui-min, CHEN Lu, CHANG Hong-tao, WANG Chuan-qing, LI Yong-tao, ZHAO Jun. Subcellular Localization and Effect on Type Ⅰ Interferon Response of Porcine Epidemic Diarrhea Virus Nsp7 [J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2017, 48(3): 501-507.