Molecular Mechanisms of PCV2 Escape from Innate Immunity

doi:10.7668/hbnxb.2018.02.021

Abstract

Abstract: To reveal the relationship between PCV2 infection and innate immune response as well as its molecular mechanism,a strain of PCV2 was adapted to PK-15 cell and PAMs,and relative fluorescence quantitative PCR assay was developed to assess the impacts of PCV2 infection,cytokines,antigen processing machineries and adaptor molecules were investigated.The results indicated that the IFN-β production was significantly suppressed during PCV2 infection in PK-15.Using luciferase reporter assays,the result showed that PCV2 infection impairs IRF3/NF-κB mediated IFN-β production. The different PCV2 expression vectors(ORF1,ORF2,or ORF3) were cotransfected with the report plasmid of the IFN-β-Luc,IRF3-Luc,NF-κB-Luc or AP-1-Luc,respectively,the luciferase reporter assays showed that the PCV2 ORF1 enhanced activation of IFN-β promoter,while IFN-β promoter was impeded by ORF2,no impact was detected by ORF3. The results showed that the inhibition of innate immunity in PCV2 could be contributed to PCV2 ORF2 by downregulating of IFN production by regulating transcription factor of IRF3 and NF-кB.

Key words: PCV2, ORF1, ORF2, Innate immunity, IFN-β

CLC Number:

S852.65

ZHANG Lei, DAI Songbao, ZHANG Lilin, SHI Peidian, WANG Jiashun, REN Jie, HUANG Jinhai. Molecular Mechanisms of PCV2 Escape from Innate Immunity[J]. ACTA AGRICULTURAE BOREALI-SINICA, 2018, 33(2): 149-156. doi: 10.7668/hbnxb.2018.02.021.

/ / Recommend / Download Citations

URL: http://www.hbnxb.net/EN/10.7668/hbnxb.2018.02.021

http://www.hbnxb.net/EN/Y2018/V33/I2/149

References

[1] Fauquet C,Fargette D.International committee on taxonomy of viruses and the 3,142 unassigned species[J].Virol J,2005,2(1):64.
[2] Park C,Jeong J,Choi K,et al.Development of porcine circovirus 2(PCV2) open reading frame 2 DNA vaccine with different adjuvants and comparison with commercial PCV2 subunit vaccine in an experimental challenge[J].Can J Vet Res,2017,81(3):171-177.
[3] Sauvage V,Cheval J,Foulongne V,et al.Identification of the first human gyrovirus,a virus related to Chicken anemia virus[J].J Virol,2011,85(15):7948-7950.
[4] Chae C.A review of porcine circovirus 2-associated syndromes and diseases[J].Vet J,2005,169(3):326-336.
[5] Gu J,Xing G,Lei J,et al.Porcine circovirus type 2 and PCV2-systemic disease-a review[J].Chinese Journal of Biotechnology,2015,31(6):880-891.
[6] 张秀娟,孙运,郭华,等.PCV2感染对仔猪肝脏MyD88-NF-κB信号途径的影响[J].南京农业大学学报,2013,36(1):97-102.
[7] 段滇宁,郭华,李晓琳,等.PCV2通过激活NF-κB信号途径调节体外培养仔猪淋巴细胞IL-4和IL-12的分泌[J].南京农业大学学报,2014,37(3):93-99.
[8] Koinig H C,Talker S C,Stadler M,et al.PCV2 vaccination induces IFN-gamma/TNF-alpha co-producing T cells with a potential role in protection[J].Vet Res,2015,46(1):1-13.
[9] 周双海,杨汉春,郭鑫,等.PCV2感染对猪MCP-1和IL-8mRNA表达的影响[J].中国兽医科学,2006,36(6):468-471.
[10] Darwich L,Balasch M,Plana-Duran J,et al.Cytokine profiles of peripheral blood mononuclear cells from pigs with postweaning multisystemic wasting syndrome in response to mitogen,superantigen or recall viral antigens[J].J Gen Virol,2003,84(12):3453-3457.
[11] García-Sastre A,Biron C A.Type 1 interferons and the virus-host relationship:a lesson in detente[J].Science,2006,312:879-882.
[12] Samuel C E.Antiviral actions of interferons[J].Clin Microbiol Rev,2001,14(4):778-809.
[13] Takaoka A,Wang Z,Choi M K,et al.DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response[J].Nature,2007,448:501-505.
[14] Makris S,Paulsen M,Johansson C.Type I interferons as regulators of lung inflammation[J].Front Immunol,2017,8:259-269.
[15] Zhang Z,Yuan B,Bao M,et al.The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells[J].Nat Immunol,2011,12(10):959-965.
[16] Sun L,Wu J,Du F,et al.Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway[J].Science,2013,339(6121):786-791.
[17] Dragan A,Carrillo R,Gerasimova T,et al.Assembling the human IFN-β enhanceosome in solution[J].J Mol Biol,2008,384(2):335-348.
[18] Hu Y,He K,Wang X.Role of Chinese herbal medicinal ingredients in secretion of cytokines by PCV2-induced endothelial cells[J].J Immunotoxicol,2016,13(2):141-147.
[19] Bowie A G,Unterholzner L.Viral evasion and subversion of pattern-recognition receptor signalling[J].Nature Reviews Immunology,2008,8(12):911-922.
[20] Sadler A J,Williams B R.Interferon-inducible antiviral effectors[J].Nature Reviews Immunology,2008,8(7):559-568.
[21] Weber F,Kochs G,Haller O.Inverse interference:how viruses fight the interferon system[J].Viral Immunol,2004,17(4):498-515.
[22] Eddicks M,Szikora F,Walhofer N,et al.Occurrence of genotypes of Porcine circovirus(PCV2) in pig farms using different vaccination strategies against PCV2[J].Tierarztl Prax Ausg G Grosstiere Nutztiere,2017,45(2):90-97.
[23] Meng X J.Porcine circovirus type 2(PCV2):Pathogenesis and interaction with the immune system[J].Annu Rev Anim Biosci,2013,1(1):43-64.
[24] Ramamoorthy S,Opriessnig T,Pal N,et al.Effect of an interferon-stimulated response element (ISRE) mutant of Porcine circovirus type 2(PCV2) on PCV2-induced pathological lesions in a Porcine reproductive and respiratory syndrome virus(PRRSV) co-infection model[J].Vet Microbiol,2011,147(1):49-58.
[25] Liu P,Li K,Garofalo R P,et al.Respiratory syncytial virus induces RelA release from cytoplasmic 100-kDa NF-κB2 complexes via a novel retinoic acid-inducible gene-I·NF-κB-inducing kinase signaling pathway[J].J Biol Chem,2008,283(34):23169-23178.
[26] Bonizzi G,Karin M.The two NF-κB activation pathways and their role in innate and adaptive immunity[J].Trends Immunol,2004,25(6):280-288.
[27] Honda K,Yanai H,Takaoka A,et al.Regulation of the type I IFN induction:a current view[J].Int Immunol,2005,17(11):1367-1378.
[28] Smith E J,MariéI,Prakash A,et al.IRF3 and IRF7 phosphorylation in virus-infected cells does not require double-stranded RNA-dependent protein kinase R or IκB kinase but is blocked by Vaccinia virus E3L protein[J].J Biol Chem,2001,276(12):8951-8957.
[29] Sun F,Zhang Y B,Liu T K,et al.Fish MITA serves as a mediator for distinct fish IFN gene activation dependent on IRF3 or IRF7[J].The Journal of Immunology,2011,187(5):2531-2539.

Please choose a citation manager

Content to export