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Co-infection with porcine bocavirus and porcine circovirus 2 affects inflammatory cytokine production and tight junctions of IPEC-J2 cells

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Abstract

Porcine bocavirus (PBoV) has a high prevalence in both healthy and diseased swine around the world. It was recently reported that PBoV and porcine circovirus type 2 (PCV2)—which contribute to porcine diarrheal disease—have a high rate of co-infection. To clarify the pathogenesis of PBoV, we examined the co-infection rate and effects of these two pathogens in IPEC-J2 porcine intestinal enterocytes. Both single and co-infection had cytopathic effects in IPEC-J2 cells. The apoptosis and proliferation rates of cells infected with both viruses did not differ significantly from those of cells infected with either one alone. PBoV and PCV2 induced the upregulation of inflammatory cytokines and the downregulation of the tight junction proteins occludin and claudin 1 in the early stage of infection, leading to destruction of epithelial barrier integrity and enhanced cytotoxicity. These findings provide insight into the pathogenic mechanisms of PBoV and PCV2 and a basis for develo** effective strategies to prevent the spread of gastrointestinal diseases in pigs and other livestock.

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References

  1. Blomstrom AL, Belak S, Fossum C, Mckillen J, Allan G, Wallgren P, Berg M (2009) Detection of a novel boca-like virus in the background of porcine circovirus type 2 induced postweaning multisytemic wasting syndrome. Virus Res 146:125–129. https://doi.org/10.1016/j.virusres.2009.09.006

    Article  CAS  PubMed  Google Scholar 

  2. Manteufel J, Truyen U (2008) Animal bocaviruses: a brief review. Intervirology 51:328–334. https://doi.org/10.1159/000173734

    Article  CAS  PubMed  Google Scholar 

  3. Zhang HB, Huang L, Liu YJ, Lin T, Sun CQ, Deng Y, Wei ZZ, Cheung AK, Long JX, Yuan SS (2011) Porcine bocaviruses: genetic analysis and prevalence in Chinese swine population. Epidemiol Infect 139:1581–1586. https://doi.org/10.1017/S0950268811000847

    Article  CAS  PubMed  Google Scholar 

  4. Shan T, Lan D, Li L, Wang C, Cui L, Zhang W, Hua X, Zhu C, Zhao W, Delwart AE (2011) Genomic characterization and high prevalence of bocaviruses in swine. PLoS ONE 6:e17292. https://doi.org/10.1371/journal.pone.0017292

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Gunn L, Collins PJ, Fanning S, Mckillen J, Morgan J, Staines A, O’Shea H (2015) Detection and characterisation of novel bocavirus (genus Bocaparvovirus) and gastroenteritis viruses from asymptomatic pigs in Ireland. Infect Ecol Epidemiol 5:27270. https://doi.org/10.3402/iee.v5.27270

    Article  PubMed  Google Scholar 

  6. Zhai S, Yue C, Wei Z, Long J, Ran D, Lin T, Deng Y, Huang L, Sun L, Zheng H (2010) High prevalence of a novel porcine bocavirus in weanling piglets with respiratory tract symptoms in China. Arch Virol 155:1313–1317. https://doi.org/10.1007/s00705-010-0698-9

    Article  CAS  PubMed  Google Scholar 

  7. Keyel PA (2014) How is inflammation initiated? Individual influences of IL-1, IL-18 and HMGB1. Cytokine 69:136–145. https://doi.org/10.1016/j.cyto.2014.03.007

    Article  CAS  PubMed  Google Scholar 

  8. Hopkins SJ (2003) The pathophysiological role of cytokines. Leg Med 5:S45–S57. https://doi.org/10.1016/S1344-6223(02)00088-3

    Article  CAS  Google Scholar 

  9. Rozycki HJ, Zhao W (2014) Interleukins for the paediatric pulmonologist. Paediatr Respir Rev 15:56–68. https://doi.org/10.1016/j.prrv.2013.04.006

    Article  PubMed  Google Scholar 

  10. Zhu X, Bai J, Liu P, Wang X, Jiang P (2016) Suppressor of cytokine signaling 3 plays an important role in porcine circovirus type 2 subclinical infection by downregulating proinflammatory responses. Sci Rep 6:32538. https://doi.org/10.1038/srep32538

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Jundi K, Greene CM (2015) Transcription of interleukin-8: how altered regulation can affect cystic fibrosis lung disease. Biomolecules 5:1386–1398. https://doi.org/10.3390/biom5031386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kobayashi Y (2008) The role of chemokines in neutrophil biology. Front Biosci 13:2400–2407. https://doi.org/10.2741/2853

    Article  CAS  PubMed  Google Scholar 

  13. Steinkasserer A, Spurr NK, Cox S, Jeggo P, Sim RB (1992) The human IL-1 receptor antagonist gene (IL1RN) maps to chromosome 2q14-q21, in the region of the IL-1 alpha and IL-1 beta loci. Genomics 13:654–657. https://doi.org/10.1016/0888-7543(92)90137-H

    Article  CAS  PubMed  Google Scholar 

  14. Khalfaoui S, Eichhorn V, Karagiannidis C, Bayh I, Brockmann M, Pieper M, Windisch W, Schildgen O, Schildgen V (2016) Lung infection by human bocavirus induces the release of profibrotic mediator cytokines in vivo and in vitro. PLoS ONE 11:e0147010. https://doi.org/10.1371/journal.pone.0147010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Liu Q, Zhang Z, Zheng Z, Zheng C, Yan L, Hu Q, Ke X, Wang H (2016) Human bocavirus NS1 and NS1-70 proteins inhibit TNF-α-mediated activation of NF-κB by targeting p65. Sci Rep 6:28481. https://doi.org/10.1038/srep28481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Nava P, López S, Arias CF, Islas S, González-Mariscal L (2004) The rotavirus surface protein VP8 modulates the gate and fence function of tight junctions in epithelial cells. J Cell Sci 117:5509–5519. https://doi.org/10.1242/jcs.01425

    Article  CAS  PubMed  Google Scholar 

  17. Luissint AC, Parkos CA, Nusrat A (2016) Inflammation and the intestinal barrier: leukocyte–epithelial cell interactions, cell junction remodeling, and mucosal repair. Gastroenterology 151:616–632. https://doi.org/10.1053/j.gastro.2016.07.008

    Article  CAS  PubMed  Google Scholar 

  18. Zhao S, Gao J, Zhu L, Yang Q (2014) Transmissible gastroenteritis virus and porcine epidemic diarrhoea virus infection induces dramatic changes in the tight junctions and microfilaments of polarized IPEC-J2 cells. Virus Res 192:34–45. https://doi.org/10.1016/j.virusres.2014.08.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. McKillen J, McNeilly F, Duffy C, McMenamy M, McNair I, Hjertner B, Millar A, McKay K, Lagan P, Adair B (2011) Isolation in cell cultures and initial characterisation of two novel bocavirus species from swine in Northern Ireland. Vet Microbiol 152:39–45. https://doi.org/10.1016/j.vetmic.2011.04.013

    Article  PubMed  Google Scholar 

  20. Li B, **ao S, Ma J, Liu Y, Li M, Wen L, Mao A, Zhang X, Ni Y, Guo R (2011) Development of a novel TaqMan-based real-time PCR assay for the detection of porcine boca-like virus (Pbo-likeV). Virol J 8:357. https://doi.org/10.1186/1743-422X-8-357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Zhao K, Han F, Zou Y, Zhu L, Li C, Xu Y, Zhang C, Tan F, Wang J, Tao S, He X, Zhou Z, Tang X (2010) Rapid detection of porcine circovirus type 2 using a TaqMan-based real-time PCR. Virol J 7:374. https://doi.org/10.1186/1743-422X-7-374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(– Delta Delta C(T)) method. Methods 25:402–408. https://doi.org/10.1006/meth.2001.1262

    Article  CAS  PubMed  Google Scholar 

  23. Zhou F, Sun H, Wang Y (2014) Porcine bocavirus: achievements in the past five years. Viruses 6:4946–4960. https://doi.org/10.3390/v6124946

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Yan M, Zhu L, Yang Q (2014) Infection of porcine circovirus 2 (PCV2) in intestinal porcine epithelial cell line (IPEC-J2) and interaction between PCV2 and IPEC-J2 microfilaments. Virol J 11:193. https://doi.org/10.1186/s12985-014-0193-0

    Article  PubMed  PubMed Central  Google Scholar 

  25. Spitzer F, Speiser S, Vahjen W, Zentek J (2016) Effect of different feed ingredients and additives on IPEC-J2 cells challenged with an enterotoxigenic Escherichia coli strain. Cytotechnology 68:1463–1471. https://doi.org/10.1007/s10616-015-9905-6

    Article  CAS  PubMed  Google Scholar 

  26. Zanello G, Meurens F, Berri M, Chevaleyre C, Melo S, Auclair E, Salmon H (2011) Saccharomyces cerevisiae decreases inflammatory responses induced by F4 + enterotoxigenic Escherichia coli in porcine intestinal epithelial cells. Vet Immunol Immunopathol 141:133–138. https://doi.org/10.1016/j.vetimm.2011.01.018

    Article  CAS  PubMed  Google Scholar 

  27. Luo Y, Chen AY, Qiu J (2011) Bocavirus infection induces a DNA damage response that facilitates viral DNA replication and mediates cell death. J Virol 85:133–145. https://doi.org/10.1128/JVI.01534-10

    Article  CAS  PubMed  Google Scholar 

  28. Krakowka S, Ellis JA, Meehan B, Kennedy S, McNeilly F, Allan G (2000) Viral wasting syndrome of swine: experimental reproduction of postweaning multisystemic wasting syndrome in gnotobiotic swine by coinfection with porcine circovirus 2 and porcine parvovirus. Vet Pathol 37:254–263. https://doi.org/10.1354/vp.37-3-254

    Article  CAS  PubMed  Google Scholar 

  29. Kim J, Ha Y, Chae C (2006) Potentiation of porcine circovirus 2-induced postweaning multisystemic wasting syndrome by porcine parvovirus is associated with excessive production of tumor necrosis factor-alpha. Vet Pathol 43:718–725. https://doi.org/10.1354/vp.43-5-718

    Article  CAS  PubMed  Google Scholar 

  30. Charo IF, Ransohoff RM (2006) The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 354:610–621. https://doi.org/10.1056/NEJMra052723

    Article  CAS  PubMed  Google Scholar 

  31. Moens E, Veldhoen M (2012) Epithelial barrier biology: good fences make good neighbours. Immunology 135:1–8. https://doi.org/10.1111/j.1365-2567.2011.03506.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Cummins PM (2012) Occludin: one protein, many forms. Mol Cell Biol 32:242–250. https://doi.org/10.1128/MCB.06029-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ferrell N, Desai RR, Fleischman AJ, Roy S, Humes HD, Fissell WH (2010) A microfluidic bioreactor with integrated transepithelial electrical resistance (TEER) measurement electrodes for evaluation of renal epithelial cells. Biotechnol Bioeng 107:707–716. https://doi.org/10.1002/bit.22835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kansagra K, Stoll B, Rognerud C, Niinikoski H, Ou CN, Harvey R (2003) Total parenteral nutrition adversely affects gut barrier function in neonatal piglets. Am J Physiol Gastrointest Liver Physiol 285:G1162–G1170. https://doi.org/10.1152/ajpgi.00243.2003

    Article  CAS  PubMed  Google Scholar 

  35. Stevenson BR, Anderson JM, Goodenough DA, Mooseker MS (1988) Tight junction structure and ZO-1 content are identical in two strains of Madin-Darby canine kidney cells which differ in transepithelial resistance. J Cell Biol 107:2401–2408. https://doi.org/10.1083/jcb.107.6.2401

    Article  CAS  PubMed  Google Scholar 

  36. Vergauwen H (2015) The IPEC-J2 cell line. In: Verhoeckx K, Cotter P, López-Expósito I, Kleiveland C, Lea T, Mackie A, Requena T, Swiatecka D, Wichers H (eds) The impact of food bioactives on health: in vitro and ex vivo models. Springer, Cham, pp 125–134

    Google Scholar 

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Acknowledgements

This work was supported by the Natural Science Foundation of China (No. 31201942). The authors thank Prof. Dingren Bi for critical advice on the project.

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Authors and Affiliations

  1. College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China

    **g Zhang, Yangchao Lu, Shaowen Li, Xugang Ku, **aoli Liu, Qigai He, Dingren Bi & **anrong Meng

  2. State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, 430070, China

    Shaowen Li, Xugang Ku, Atta Muhammad Memon, Qigai He, Dingren Bi & **anrong Meng

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  1. **g Zhang
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Contributions

JZ and XrM designed the experiments and carried out molecular and statistical analyses. JZ performed the experiments and drafted the manuscript. YcL and AMM revised the manuscript. LxL performed the HE staining experiment. DrB, SwL, QgH, and XgK provided useful suggestions for the project. All authors read and approved the final manuscript.

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Correspondence to **anrong Meng.

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This article does not contain any studies with animals that required ethical approval.

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Edited by Juergen A Richt.

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Zhang, J., Lu, Y., Li, S. et al. Co-infection with porcine bocavirus and porcine circovirus 2 affects inflammatory cytokine production and tight junctions of IPEC-J2 cells. Virus Genes 54, 684–693 (2018). https://doi.org/10.1007/s11262-018-1596-6

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