1887

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) usually establishes a prolonged infection and causes an immunosuppressive state. It has been proposed that IL-10 plays an important role in PRRSV-induced immunosuppression. However, this mechanism has not been completely elucidated. In this study, we found that transfection of 3D4/2 macrophages with the N protein gene of type 2 PRRSV significantly upregulated IL-10 expression at the transcriptional level. Moreover, alanine substitution mutation analysis revealed that the N protein residues 33–37, 65–68 and 112–123 were related to the upregulation of IL-10 promoter activity. Recombinant PRRSV with mutations at residues 33–37 in the N protein (rQ33-5A and rS36A) recovered from corresponding infectious cDNA clones and induced significantly lower levels of IL-10 production in infected monocyte-derived dendritic cells, as compared with their revertants rQ33-5A(R) and rS36A(R), and the wild-type recombinant PRRSV strain rNT/wt. These data indicate that the type 2 PRRSV N protein plays an important role in IL-10 induction and the N-N non-covalent domain is associated with this activity.

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2015-06-01
2020-09-21
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References

  1. Burgara-Estrella A., Díaz I., Rodríguez-Gómez I. M., Essler S. E., Hernández J., Mateu E. 2013; Predicted peptides from non-structural proteins of porcine reproductive and respiratory syndrome virus are able to induce IFN-γ and IL-10. Viruses 5:663–677 [CrossRef][PubMed]
    [Google Scholar]
  2. Chang H. C., Peng Y. T., Chang H. L., Chaung H. C., Chung W. B. 2008; Phenotypic and functional modulation of bone marrow-derived dendritic cells by porcine reproductive and respiratory syndrome virus. Vet Microbiol 129:281–293 [CrossRef][PubMed]
    [Google Scholar]
  3. Charerntantanakul W., Kasinrerk W. 2010; Interleukin-10 antisense oligodeoxynucleotide suppresses IL-10 expression and effects on proinflammatory cytokine responses to porcine reproductive and respiratory syndrome virus. Viral Immunol 23:425–435 [CrossRef][PubMed]
    [Google Scholar]
  4. Charerntantanakul W., Kasinrerk W. 2012; Plasmids expressing interleukin-10 short hairpin RNA mediate IL-10 knockdown and enhance tumor necrosis factor alpha and interferon gamma expressions in response to porcine reproductive and respiratory syndrome virus. Vet Immunol Immunopathol 146:159–168 [CrossRef][PubMed]
    [Google Scholar]
  5. 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]
  6. Choi H. W., Nam E., Lee Y. J., Noh Y. H., Lee S. C., Yoon I. J., Kim H. S., Kang S. Y., Choi Y. K., Lee C. 2014; Genomic analysis and pathogenic characteristics of Type 2 porcine reproductive and respiratory syndrome virus nsp2 deletion strains isolated in Korea. Vet Microbiol 170:232–245 [CrossRef][PubMed]
    [Google Scholar]
  7. Dauer M., Obermaier B., Herten J., Haerle C., Pohl K., Rothenfusser S., Schnurr M., Endres S., Eigler A. 2003; Mature dendritic cells derived from human monocytes within 48 hours: a novel strategy for dendritic cell differentiation from blood precursors. J Immunol 170:4069–4076 [CrossRef][PubMed]
    [Google Scholar]
  8. Dauer M., Schad K., Herten J., Junkmann J., Bauer C., Kiefl R., Endres S., Eigler A. 2005; FastDC derived from human monocytes within 48 h effectively prime tumor antigen-specific cytotoxic T cells. J Immunol Methods 302:145–155 [CrossRef][PubMed]
    [Google Scholar]
  9. Díaz-San Segundo F., Rodríguez-Calvo T., de Avila A., Sevilla N. 2009; Immunosuppression during acute infection with foot-and-mouth disease virus in swine is mediated by IL-10. PLoS ONE 4:e5659 [CrossRef][PubMed]
    [Google Scholar]
  10. 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]
  11. Donnelly R. P., Sheikh F., Kotenko S. V., Dickensheets H. 2004; The expanded family of class II cytokines that share the IL-10 receptor-2 (IL-10R2) chain. J Leukoc Biol 76:314–321 [CrossRef][PubMed]
    [Google Scholar]
  12. Firth A. E., Zevenhoven-Dobbe J. C., Wills N. M., Go Y. Y., Balasuriya U. B., Atkins J. F., Snijder E. J., Posthuma C. C. 2011; Discovery of a small arterivirus gene that overlaps the GP5 coding sequence and is important for virus production. J Gen Virol 92:1097–1106 [CrossRef][PubMed]
    [Google Scholar]
  13. Flores-Mendoza L., Silva-Campa E., Reséndiz M., Osorio F. A., Hernández J. 2008; Porcine reproductive and respiratory syndrome virus infects mature porcine dendritic cells and up-regulates interleukin-10 production. Clin Vaccine Immunol 15:720–725 [CrossRef][PubMed]
    [Google Scholar]
  14. Fu Y., Quan R., Zhang H., Hou J., Tang J., Feng W. H. 2012; Porcine reproductive and respiratory syndrome virus induces interleukin-15 through the NF-κB signaling pathway. J Virol 86:7625–7636 [CrossRef][PubMed]
    [Google Scholar]
  15. 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]
  16. Gómez-Laguna J., Salguero F. J., Barranco I., Pallarés F. J., Rodríguez-Gómez I. M., Bernabé A., Carrasco L. 2010; Cytokine expression by macrophages in the lung of pigs infected with the porcine reproductive and respiratory syndrome virus. J Comp Pathol 142:51–60 [CrossRef][PubMed]
    [Google Scholar]
  17. Gómez-Laguna J., Salguero F. J., Pallarés F. J., Carrasco L. 2013; Immunopathogenesis of porcine reproductive and respiratory syndrome in the respiratory tract of pigs. Vet J 195:148–155 [CrossRef][PubMed]
    [Google Scholar]
  18. Guan X., Peng J. R., Yuan L., Wang H., Wei Y. H., Leng X. S. 2004; A novel, rapid strategy to form dendritomas from human dendritic cells and hepatocellular carcinoma cell line HCCLM3 cells using mature dendritic cells derived from human peripheral blood CD14+ monocytes within 48 hours of in vitro culture. World J Gastroenterol 10:3564–3568[PubMed]
    [Google Scholar]
  19. Guo B., Lager K. M., Henningson J. N., Miller L. C., Schlink S. N., Kappes M. A., Kehrli M. E. Jr, Brockmeier S. L., Nicholson T. L. et al. 2013; Experimental infection of United States swine with a Chinese highly pathogenic strain of porcine reproductive and respiratory syndrome virus. Virology 435:372–384 [CrossRef][PubMed]
    [Google Scholar]
  20. Iannone F., De Bari C., Dell’Accio F., Covelli M., Cantatore F. P., Patella V., Lo Bianco G., Lapadula G. 2001; Interleukin-10 and interleukin-10 receptor in human osteoarthritic and healthy chondrocytes. Clin Exp Rheumatol 19:139–145[PubMed]
    [Google Scholar]
  21. Johnson C. R., Griggs T. F., Gnanandarajah J., Murtaugh M. P. 2011; Novel structural protein in porcine reproductive and respiratory syndrome virus encoded by an alternative ORF5 present in all arteriviruses. J Gen Virol 92:1107–1116 [CrossRef][PubMed]
    [Google Scholar]
  22. Kawai T., Akira S. 2007; TLR signaling. Semin Immunol 19:24–32 [CrossRef][PubMed]
    [Google Scholar]
  23. Klinge K. L., Vaughn E. M., Roof M. B., Bautista E. M., Murtaugh M. P. 2009; Age-dependent resistance to Porcine reproductive and respiratory syndrome virus replication in swine. Virol J 6:177 [CrossRef][PubMed]
    [Google Scholar]
  24. Koponen P., Karjalainen M. K., Korppi M. 2013; IL10 polymorphisms, rhinovirus-induced bronchiolitis, and childhood asthma. J Allergy Clin Immunol 131:249–250 [CrossRef][PubMed]
    [Google Scholar]
  25. Lawson S. R., Li Y., Patton J. B., Langenhorst R. J., Sun Z., Jiang Z., Christopher-Hennings J., Nelson E. A., Knudsen D. et al. 2012; Interleukin-1β expression by a recombinant porcine reproductive and respiratory syndrome virus. Virus Res 163:461–468 [CrossRef][PubMed]
    [Google Scholar]
  26. Lee C., Calvert J. G., Welch S. K., Yoo D. 2005; A DNA-launched reverse genetics system for porcine reproductive and respiratory syndrome virus reveals that homodimerization of the nucleocapsid protein is essential for virus infectivity. Virology 331:47–62 [CrossRef][PubMed]
    [Google Scholar]
  27. Liu J., Zhan W., Kim C. J., Clayton K., Zhao H., Lee E., Cao J. C., Ziegler B., Gregor A. et al. 2014; IL-10-producing B cells are induced early in HIV-1 infection and suppress HIV-1-specific T cell responses. PLoS ONE 9:e89236 [CrossRef][PubMed]
    [Google Scholar]
  28. Loebbermann J., Schnoeller C., Thornton H., Durant L., Sweeney N. P., Schuijs M., O’Garra A., Johansson C., Openshaw P. J. 2012; IL-10 regulates viral lung immunopathology during acute respiratory syncytial virus infection in mice. PLoS ONE 7:e32371 [CrossRef][PubMed]
    [Google Scholar]
  29. López-Fuertes L., Campos E., Doménech N., Ezquerra A., Castro J. M., Domínguez J., Alonso F. 2000; Porcine reproductive and respiratory syndrome (PRRS) virus down-modulates TNF-alpha production in infected macrophages. Virus Res 69:41–46 [CrossRef][PubMed]
    [Google Scholar]
  30. Luo R., Fang L., Jiang Y., Jin H., Wang Y., Wang D., Chen H., Xiao S. 2011; Activation of NF-κB by nucleocapsid protein of the porcine reproductive and respiratory syndrome virus. Virus Genes 42:76–81 [CrossRef][PubMed]
    [Google Scholar]
  31. Lupfer C., Kanneganti T. D. 2013; The expanding role of NLRs in antiviral immunity. Immunol Rev 255:13–24 [CrossRef][PubMed]
    [Google Scholar]
  32. Magatti M., Caruso M., De Munari S., Vertua E., De D., Manuelpillai U., Parolini O. 2014; Human amniotic membrane-derived mesenchymal and epithelial cells exert different effects on monocyte-derived dendritic cell differentiation and function. Cell Transplant doi:10.3727/096368914X684033 [Epub ahead of print] [PubMed]
    [Google Scholar]
  33. Mason G. M., Jackson S., Okecha G., Poole E., Sissons J. G., Sinclair J., Wills M. R. 2013; Human cytomegalovirus latency-associated proteins elicit immune-suppressive IL-10 producing CD4+ T cells. PLoS Pathog 9:e1003635 [CrossRef][PubMed]
    [Google Scholar]
  34. Mateu E., Diaz I. 2008; The challenge of PRRS immunology. Vet J 177:345–351 [CrossRef][PubMed]
    [Google Scholar]
  35. Meng X. J., Paul P. S., Halbur P. G., Lum M. A. 1995; Phylogenetic analyses of the putative M (ORF 6) and N (ORF 7) genes of porcine reproductive and respiratory syndrome virus (PRRSV): implication for the existence of two genotypes of PRRSV in the U.S.A. and Europe. Arch Virol 140:745–755 [CrossRef][PubMed]
    [Google Scholar]
  36. Ng T. H., Britton G. J., Hill E. V., Verhagen J., Burton B. R., Wraith D. C. 2013; Regulation of adaptive immunity; the role of interleukin-10. Front Immunol 4:129 [CrossRef][PubMed]
    [Google Scholar]
  37. 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]
  38. Quan R., Fu Y., He W., Feng W. H. 2012; Cloning and characterization of the porcine IL-10 promoter. Vet Immunol Immunopathol 146:277–282 [CrossRef][PubMed]
    [Google Scholar]
  39. Redpath S., Ghazal P., Gascoigne N. R. 2001; Hijacking and exploitation of IL-10 by intracellular pathogens. Trends Microbiol 9:86–92 [CrossRef][PubMed]
    [Google Scholar]
  40. Rodriguez M. J., Sarraseca J., Garcia J., Sanz A., Plana-Durán J., Ignacio Casal J. 1997; Epitope mapping of the nucleocapsid protein of European and North American isolates of porcine reproductive and respiratory syndrome virus. J Gen Virol 78:2269–2278[PubMed] [CrossRef]
    [Google Scholar]
  41. Roquilly A., Broquet A., Jacqueline C., Masson D., Segain J. P., Braudeau C., Vourc’h M., Caillon J., Altare F. et al. 2014; Hydrocortisone prevents immunosuppression by interleukin-10+ natural killer cells after trauma-hemorrhage. Crit Care Med 42:e752–e761 [CrossRef][PubMed]
    [Google Scholar]
  42. Rowland R. R., Yoo D. 2003; Nucleolar-cytoplasmic shuttling of PRRSV nucleocapsid protein: a simple case of molecular mimicry or the complex regulation by nuclear import, nucleolar localization and nuclear export signal sequences. Virus Res 95:23–33 [CrossRef][PubMed]
    [Google Scholar]
  43. Rowland R. R., Schneider P., Fang Y., Wootton S., Yoo D., Benfield D. A. 2003; Peptide domains involved in the localization of the porcine reproductive and respiratory syndrome virus nucleocapsid protein to the nucleolus. Virology 316:135–145 [CrossRef][PubMed]
    [Google Scholar]
  44. Sagong M., Lee C. 2011; Porcine reproductive and respiratory syndrome virus nucleocapsid protein modulates interferon-β production by inhibiting IRF3 activation in immortalized porcine alveolar macrophages. Arch Virol 156:2187–2195 [CrossRef][PubMed]
    [Google Scholar]
  45. Snijder E. J., Meulenberg J. J. 1998; The molecular biology of arteriviruses. J Gen Virol 79:961–979[PubMed] [CrossRef]
    [Google Scholar]
  46. Snijder E. J., Kikkert M., Fang Y. 2013; Arterivirus molecular biology and pathogenesis. J Gen Virol 94:2141–2163 [CrossRef][PubMed]
    [Google Scholar]
  47. Song S., Bi J., Wang D., Fang L., Zhang L., Li F., Chen H., Xiao S. 2013; Porcine reproductive and respiratory syndrome virus infection activates IL-10 production through NF-κB and p38 MAPK pathways in porcine alveolar macrophages. Dev Comp Immunol 39:265–272 [CrossRef][PubMed]
    [Google Scholar]
  48. Subramaniam S., Kwon B., Beura L. K., Kuszynski C. A., Pattnaik A. K., Osorio F. A. 2010; Porcine reproductive and respiratory syndrome virus non-structural protein 1 suppresses tumor necrosis factor-alpha promoter activation by inhibiting NF-κB and Sp1. Virology 406:270–279 [CrossRef][PubMed]
    [Google Scholar]
  49. Subramaniam S., Beura L. K., Kwon B., Pattnaik A. K., Osorio F. A. 2012; Amino acid residues in the non-structural protein 1 of porcine reproductive and respiratory syndrome virus involved in down-regulation of TNF-α expression in vitro and attenuation in vivo. Virology 432:241–249 [CrossRef][PubMed]
    [Google Scholar]
  50. 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]
  51. 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]
  52. Thanawongnuwech R., Young T. F., Thacker B. J., Thacker E. L. 2001; Differential production of proinflammatory cytokines: in vitro PRRSV and Mycoplasma hyopneumoniae co-infection model. Vet Immunol Immunopathol 79:115–127 [CrossRef][PubMed]
    [Google Scholar]
  53. Thanawongnuwech R., Thacker B., Halbur P., Thacker E. L. 2004; Increased production of proinflammatory cytokines following infection with porcine reproductive and respiratory syndrome virus and Mycoplasma hyopneumoniae . Clin Diagn Lab Immunol 11:901–908[PubMed]
    [Google Scholar]
  54. Tian D., Zheng H., Zhang R., Zhuang J., Yuan S. 2011; Chimeric porcine reproductive and respiratory syndrome viruses reveal full function of genotype 1 envelope proteins in the backbone of genotype 2. Virology 412:1–8 [CrossRef][PubMed]
    [Google Scholar]
  55. Wang X., Eaton M., Mayer M., Li H., He D., Nelson E., Christopher-Hennings J. 2007; Porcine reproductive and respiratory syndrome virus productively infects monocyte-derived dendritic cells and compromises their antigen-presenting ability. Arch Virol 152:289–303 [CrossRef][PubMed]
    [Google Scholar]
  56. Wongyanin P., Buranapraditkul S., Yoo D., Thanawongnuwech R., Roth J. A., Suradhat S. 2012; Role of porcine reproductive and respiratory syndrome virus nucleocapsid protein in induction of interleukin-10 and regulatory T-lymphocytes (Treg). J Gen Virol 93:1236–1246 [CrossRef][PubMed]
    [Google Scholar]
  57. 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]
  58. Wootton S. K., Rowland R. R., Yoo D. 2002; Phosphorylation of the porcine reproductive and respiratory syndrome virus nucleocapsid protein. J Virol 76:10569–10576 [CrossRef][PubMed]
    [Google Scholar]
  59. Xie L., Choudhury G. R., Winters A., Yang S. H., Jin K. 2015; Cerebral regulatory T cells restrain microglia/macrophage-mediated inflammatory responses via IL-10. Eur J Immunol 45:180–191 [CrossRef][PubMed]
    [Google Scholar]
  60. Zhang R., Chen C., Sun Z., Tan F., Zhuang J., Tian D., Tong G., Yuan S. 2012; Disulfide linkages mediating nucleocapsid protein dimerization are not required for porcine arterivirus infectivity. J Virol 86:4670–4681 [CrossRef][PubMed]
    [Google Scholar]
  61. Zhang L., Liu J., Bai J., Wang X., Li Y., Jiang P. 2013; Comparative expression of Toll-like receptors and inflammatory cytokines in pigs infected with different virulent porcine reproductive and respiratory syndrome virus isolates. Virol J 10:135 [CrossRef][PubMed]
    [Google Scholar]
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