1887

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) infection induces interleukin (IL)-10 production and increased numbers of PRRSV-specific regulatory T-lymphocytes in infected pigs. In the present study, the roles of the nucleocapsid (N) protein in induction of IL-10 and CD4CD25Foxp3 lymphocytes (T) were investigated. Transfection of porcine monocyte-derived dendritic cells (MoDCs) and pulmonary alveolar macrophages (PAMs) with a plasmid encoding N protein resulted in significant upregulation of IL-10 gene expression in the gene-transfected cells. Structural conformation, but not nuclear localization, of the expressed N protein was indicated to be essential for the ability to induce IL-10. Furthermore, the presence of recombinant N proteins in cultured PBMCs increased the number of IL-10-producing lymphocytes. Strong induction of IL-10-producing cells and T was observed when using N protein-pulsed MoDCs, suggesting an important role of MoDCs in induction of IL-10 and T by the N protein. Neutralization of IL-10 by addition of an anti-IL-10 antibody in the culture system resulted in marked reduction of PRRSV-induced T in the cultured PBMCs. Together, the data demonstrate the immunomodulatory properties of the PRRSV N protein and the linkage between IL-10 production and development of PRRSV-induced T. Our results reveal an immunomodulatory function of the PRRSV N protein that may contribute to the unique immunological outcome observed following PRRSV infection.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.040287-0
2012-06-01
2021-05-11
Loading full text...

Full text loading...

/deliver/fulltext/jgv/93/6/1236.html?itemId=/content/journal/jgv/10.1099/vir.0.040287-0&mimeType=html&fmt=ahah

References

  1. Aborsangaya K. B., Dembinski I., Khatkar S., Alphonse M. P., Nickerson P., Rempel J. D. 2007; Impact of aboriginal ethnicity on HCV core-induced IL-10 synthesis: interaction with IL-10 gene polymorphisms. Hepatology 45:623–630 [CrossRef][PubMed]
    [Google Scholar]
  2. Barrett L., Gallant M., Howley C., Bowmer M. I., Hirsch G., Peltekian K., Grant M. 2008; Enhanced IL-10 production in response to hepatitis C virus proteins by peripheral blood mononuclear cells from human immunodeficiency virus-monoinfected individuals. BMC Immunol 9:28 [CrossRef][PubMed]
    [Google Scholar]
  3. Cavanagh D. 1997; Nidovirales: a new order comprising Coronaviridae and Arteriviridae . Arch Virol 142:629–633[PubMed]
    [Google Scholar]
  4. Charerntantanakul W., Platt R., Roth J. A. 2006; Effects of porcine reproductive and respiratory syndrome virus-infected antigen-presenting cells on T cell activation and antiviral cytokine production. Viral Immunol 19:646–661 [CrossRef][PubMed]
    [Google Scholar]
  5. Chung H.-K., Chae C. 2003; Expression of interleukin-10 and interleukin-12 in piglets experimentally infected with porcine reproductive and respiratory syndrome virus (PRRSV). J Comp Pathol 129:205–212 [CrossRef][PubMed]
    [Google Scholar]
  6. De Bruin M. G. M., Samsom J. N., Voermans J. J. M., van Rooij E. M. A., De Visser Y. E., Bianchi A. T. J. 2000; Effects of a porcine reproductive and respiratory syndrome virus infection on the development of the immune response against pseudorabies virus. Vet Immunol Immunopathol 76:125–135 [CrossRef][PubMed]
    [Google Scholar]
  7. Doan D. N., Dokland T. 2003; Structure of the nucleocapsid protein of porcine reproductive and respiratory syndrome virus. Structure 11:1445–1451 [CrossRef][PubMed]
    [Google Scholar]
  8. Dolganiuc A., Kodys K., Kopasz A., Marshall C., Do T., Romics L. J. Jr, Mandrekar P., Zapp M., Szabo G. 2003; Hepatitis C virus core and nonstructural protein 3 proteins induce pro- and anti-inflammatory cytokines and inhibit dendritic cell differentiation. J Immunol 170:5615–5624[PubMed] [CrossRef]
    [Google Scholar]
  9. Genini S., Delputte P. L., Malinverni R., Cecere M., Stella A., Nauwynck H. J., Giuffra E. 2008; Genome-wide transcriptional response of primary alveolar macrophages following infection with porcine reproductive and respiratory syndrome virus. J Gen Virol 89:2550–2564 [CrossRef][PubMed]
    [Google Scholar]
  10. Gómez-Laguna J., Rodríguez-Gómez I. M., Barranco I., Pallarés F. J., Salguero F. J., Bernabé A., Carrasco L. 2010; IL-10 and TGFβ expression in the lung and tonsil of pigs experimentally infected with porcine reproductive and respiratory syndrome virus. In Proceedings of the 21st International Pig Veterinary Society (IPVS) Congress, Vancouver, Canada p. 147 Edited by S. D’ Allaire, R. Friendship.
    [Google Scholar]
  11. Hao D., He L. X., Qu J. M., Pan J., Hu B. J., Zhang J., Li Z. Z. 2005; [A study of pulmonary inflammatory reaction induced by N-protein of SARS-CoV in rat models and effects of glucocorticoids on it]. Zhonghua Nei Ke Za Zhi 44:890–893 (in Chinese) [PubMed]
    [Google Scholar]
  12. Käser T., Gerner W., Hammer S. E., Patzl M., Saalmüller A. 2008; Detection of Foxp3 protein expression in porcine T lymphocytes. Vet Immunol Immunopathol 125:92–101 [CrossRef][PubMed]
    [Google Scholar]
  13. Kitikoon P., Vincent A. L., Jones K. R., Nilubol D., Yu S., Janke B. H., Thacker B. J., Thacker E. L. 2009; Vaccine efficacy and immune response to swine influenza virus challenge in pigs infected with porcine reproductive and respiratory syndrome virus at the time of SIV vaccination. Vet Microbiol 139:235–244 [CrossRef][PubMed]
    [Google Scholar]
  14. Lechner F., Wong D. K., Dunbar P. R., Chapman R., Chung R. T., Dohrenwend P., Robbins G., Phillips R., Klenerman P., Walker B. D. 2000; Analysis of successful immune responses in persons infected with hepatitis C virus. J Exp Med 191:1499–1512 [CrossRef][PubMed]
    [Google Scholar]
  15. Lee C., Hodgins D., Calvert J. G., Welch S. K., Jolie R., Yoo D. 2006; Mutations within the nuclear localization signal of the porcine reproductive and respiratory syndrome virus nucleocapsid protein attenuate virus replication. Virology 346:238–250 [CrossRef][PubMed]
    [Google Scholar]
  16. LeRoith T., Hammond S., Todd S. M., Ni Y., Cecere T., Pelzer K. D. 2011; A modified live PRRSV vaccine and the pathogenic parent strain induce regulatory T cells in pigs naturally infected with Mycoplasma hyopneumoniae . Vet Immunol Immunopathol 140:312–316 [CrossRef][PubMed]
    [Google Scholar]
  17. Lopez O. J., Osorio F. A. 2004; Role of neutralizing antibodies in PRRSV protective immunity. Vet Immunol Immunopathol 102:155–163 [CrossRef][PubMed]
    [Google Scholar]
  18. Meier W. A., Galeota J., Osorio F. A., Husmann R. J., Schnitzlein W. M., Zuckermann F. A. 2003; Gradual development of the interferon-gamma response of swine to porcine reproductive and respiratory syndrome virus infection or vaccination. Virology 309:18–31 [CrossRef][PubMed]
    [Google Scholar]
  19. Meng X. J. 2000; Heterogeneity of porcine reproductive and respiratory syndrome virus: implications for current vaccine efficacy and future vaccine development. Vet Microbiol 74:309–329 [CrossRef][PubMed]
    [Google Scholar]
  20. Meulenberg J. J. 2000; PRRSV, the virus. Vet Res 31:11–21 [CrossRef][PubMed]
    [Google Scholar]
  21. Moore K. W., de Waal Malefyt R., Coffman R. L., O’Garra A. 2001; Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19:683–765 [CrossRef][PubMed]
    [Google Scholar]
  22. Murtaugh M. P., Xiao Z., Zuckermann F. 2002; Immunological responses of swine to porcine reproductive and respiratory syndrome virus infection. Viral Immunol 15:533–547 [CrossRef][PubMed]
    [Google Scholar]
  23. Park J. Y., Kim H. S., Seo S. H. 2008; Characterization of interaction between porcine reproductive and respiratory syndrome virus and porcine dendritic cells. J Microbiol Biotechnol 18:1709–1716[PubMed]
    [Google Scholar]
  24. Pei Y., Hodgins D. C., Lee C., Calvert J. G., Welch S. K., Jolie R., Keith M., Yoo D. 2008; Functional mapping of the porcine reproductive and respiratory syndrome virus capsid protein nuclear localization signal and its pathogenic association. Virus Res 135:107–114 [CrossRef][PubMed]
    [Google Scholar]
  25. Peng Y. T., Chaung H. C., Chang H. L., Chang H. C., Chung W. B. 2009; Modulations of phenotype and cytokine expression of porcine bone marrow-derived dendritic cells by porcine reproductive and respiratory syndrome virus. Vet Microbiol 136:359–365 [CrossRef][PubMed]
    [Google Scholar]
  26. Royaee A. R., Husmann R. J., Dawson H. D., Calzada-Nova G., Schnitzlein W. M., Zuckermann F. A., Lunney J. K. 2004; Deciphering the involvement of innate immune factors in the development of the host response to PRRSV vaccination. Vet Immunol Immunopathol 102:199–216 [CrossRef][PubMed]
    [Google Scholar]
  27. Sakaguchi S. 2004; Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 22:531–562 [CrossRef][PubMed]
    [Google Scholar]
  28. Silva-Campa E., Flores-Mendoza L., Reséndiz M., Pinelli-Saavedra A., Mata-Haro V., Mwangi W., Hernández J. 2009; Induction of T helper 3 regulatory cells by dendritic cells infected with porcine reproductive and respiratory syndrome virus. Virology 387:373–379 [CrossRef][PubMed]
    [Google Scholar]
  29. Silva-Campa E., Cordoba L., Fraile L., Flores-Mendoza L., Montoya M., Hernández J. 2010; European genotype of porcine reproductive and respiratory syndrome (PRRSV) infects monocyte-derived dendritic cells but does not induce Treg cells. Virology 396:264–271 [CrossRef][PubMed]
    [Google Scholar]
  30. Snijder E. J., Meulenberg J. J. 1998; The molecular biology of arteriviruses. J Gen Virol 79:961–979[PubMed]
    [Google Scholar]
  31. Song C., Krell P., Yoo D. 2010; Nonstructural protein 1α subunit-based inhibition of NF-κB activation and suppression of interferon-β production by porcine reproductive and respiratory syndrome virus. Virology 407:268–280 [CrossRef][PubMed]
    [Google Scholar]
  32. Subramaniam S., Sur J. H., Kwon B., Pattnaik A. K., Osorio F. A. 2011; A virulent strain of porcine reproductive and respiratory syndrome virus does not up-regulate interleukin-10 levels in vitro or in vivo. Virus Res 155:415–422 [CrossRef][PubMed]
    [Google Scholar]
  33. Suradhat S., Thanawongnuwech R. 2003; Upregulation of interleukin-10 gene expression in the leukocytes of pigs infected with porcine reproductive and respiratory syndrome virus. J Gen Virol 84:2755–2760 [CrossRef][PubMed]
    [Google Scholar]
  34. Suradhat S., Thanawongnuwech R., Poovorawan Y. 2003; Upregulation of IL-10 gene expression in porcine peripheral blood mononuclear cells by porcine reproductive and respiratory syndrome virus. J Gen Virol 84:453–459 [CrossRef][PubMed]
    [Google Scholar]
  35. Suradhat S., Kesdangsakonwut S., Sada W., Buranapraditkun S., Wongsawang S., Thanawongnuwech R. 2006; Negative impact of porcine reproductive and respiratory syndrome virus infection on the efficacy of classical swine fever vaccine. Vaccine 24:2634–2642 [CrossRef][PubMed]
    [Google Scholar]
  36. Thacker E. L., Thacker B. J., Young T. F., Halbur P. G. 2000; Effect of vaccination on the potentiation of porcine reproductive and respiratory syndrome virus (PRRSV)-induced pneumonia by Mycoplasma hyopneumoniae . Vaccine 18:1244–1252 [CrossRef][PubMed]
    [Google Scholar]
  37. Thanawongnuwech R., Suradhat S. 2010; Taming PRRSV: revisiting the control strategies and vaccine design. Virus Res 154:133–140 [CrossRef][PubMed]
    [Google Scholar]
  38. Thanawongnuwech R., Thacker E. L. 2003; Interleukin-10, interleukin-12, and interferon- γ levels in the respiratory tract following Mycoplasma hyopneumoniae and PRRSV infection in pigs. Viral Immunol 16:357–367 [CrossRef][PubMed]
    [Google Scholar]
  39. Thanawongnuwech R., Halbur P. G., Ackermann M. R., Thacker E. L., Royer R. L. 1998; Effects of low (modified-live virus vaccine) and high (VR-2385)-virulence strains of porcine reproductive and respiratory syndrome virus on pulmonary clearance of copper particles in pigs. Vet Pathol 35:398–406 [CrossRef][PubMed]
    [Google Scholar]
  40. Thanawongnuwech R., Brown G. B., Halbur P. G., Roth J. A., Royer R. L., Thacker B. J. 2000; Pathogenesis of porcine reproductive and respiratory syndrome virus-induced increase in susceptibility to Streptococcus suis infection. Vet Pathol 37:143–152 [CrossRef][PubMed]
    [Google Scholar]
  41. Thanawongnuwech R., Amonsin A., Tatsanakit A., Damrongwatanapokin S. 2004; Genetics and geographical variation of porcine reproductive and respiratory syndrome virus (PRRSV) in Thailand. Vet Microbiol 101:9–21 [CrossRef][PubMed]
    [Google Scholar]
  42. Thimme R., Oldach D., Chang K. M., Steiger C., Ray S. C., Chisari F. V. 2001; Determinants of viral clearance and persistence during acute hepatitis C virus infection. J Exp Med 194:1395–1406 [CrossRef][PubMed]
    [Google Scholar]
  43. Van Gucht S., Labarque G., Van Reeth K. 2004; The combination of PRRS virus and bacterial endotoxin as a model for multifactorial respiratory disease in pigs. Vet Immunol Immunopathol 102:165–178 [CrossRef][PubMed]
    [Google Scholar]
  44. van Reeth K., Nauwynck H. 2000; Proinflammatory cytokines and viral respiratory disease in pigs. Vet Res 31:187–213 [CrossRef][PubMed]
    [Google Scholar]
  45. Wang H. Y., Wang R. F. 2007; Regulatory T cells and cancer. Curr Opin Immunol 19:217–223 [CrossRef][PubMed]
    [Google Scholar]
  46. Wongyanin P., Buranapraditkun S., Chokeshai-Usaha K., Thanawonguwech R., Suradhat S. 2010; Induction of inducible CD4+CD25+Foxp3+ regulatory T lymphocytes by porcine reproductive and respiratory syndrome virus (PRRSV). Vet Immunol Immunopathol 133:170–182 [CrossRef][PubMed]
    [Google Scholar]
  47. Wootton S. K., Nelson E. A., Yoo D. 1998; Antigenic structure of the nucleocapsid protein of porcine reproductive and respiratory syndrome virus. Clin Diagn Lab Immunol 5:773–779[PubMed]
    [Google Scholar]
  48. Zhao P., Cao J., Zhao L. J., Qin Z. L., Ke J. S., Pan W., Ren H., Yu J. G., Qi Z. T. 2005; Immune responses against SARS-coronavirus nucleocapsid protein induced by DNA vaccine. Virology 331:128–135 [CrossRef][PubMed]
    [Google Scholar]
  49. Zheng N., Xia R., Yang C., Yin B., Li Y., Duan C., Liang L., Guo H., Xie Q. 2009; Boosted expression of the SARS-CoV nucleocapsid protein in tobacco and its immunogenicity in mice. Vaccine 27:5001–5007 [CrossRef][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.040287-0
Loading
/content/journal/jgv/10.1099/vir.0.040287-0
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error