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.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.000061
2015-06-01
2019-10-14
Loading full text...

Full text loading...

/deliver/fulltext/jgv/96/6/1276.html?itemId=/content/journal/jgv/10.1099/vir.0.000061&mimeType=html&fmt=ahah

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]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.000061
Loading
/content/journal/jgv/10.1099/vir.0.000061
Loading

Data & Media loading...

Supplementary Data



PDF

Most Cited This Month

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