1887

Abstract

Classical swine fever virus (CSFV) has a tropism for vascular endothelial cells and immune system cells. The process and release of pro-inflammatory cytokines, including IL-1β and IL-18, is one of the fundamental reactions of the innate immune response to viral infection. In this study, we investigated the production of IL-1β from macrophages following CSFV infection. Our results showed that IL-1β was upregulated after CSFV infection through activating caspase-1. Subsequent studies demonstrated that reactive oxygen species may not be involved in CSFV-mediated IL-1β release. Recently, research has indicated a novel mechanism by which inflammasomes are triggered through detection of activity of viroporin. We further demonstrated that CSFV viroporin p7 protein induced IL-1β secretion which could be inhibited by the ion channel blocker amantadine and also discovered that p7 protein was a short-lived protein degraded by the proteasome. Together, our observations provided an insight into the mechanism of CSFV-induced inflammatory responses.

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2014-12-01
2019-11-22
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References

  1. Allen I. C., Scull M. A., Moore C. B., Holl E. K., McElvania-TeKippe E., Taxman D. J., Guthrie E. H., Pickles R. J., Ting J. P.-Y.. ( 2009;). The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA. . Immunity 30:, 556–565. [CrossRef][PubMed]
    [Google Scholar]
  2. Becher P., Avalos Ramirez R., Orlich M., Cedillo Rosales S., König M., Schweizer M., Stalder H., Schirrmeier H., Thiel H. J.. ( 2003;). Genetic and antigenic characterization of novel pestivirus genotypes: implications for classification. . Virology 311:, 96–104. [CrossRef][PubMed]
    [Google Scholar]
  3. Bentham M. J., Foster T. L., McCormick C., Griffin S.. ( 2013;). Mutations in hepatitis C virus p7 reduce both the egress and infectivity of assembled particles via impaired proton channel function. . J Gen Virol 94:, 2236–2248. [CrossRef][PubMed]
    [Google Scholar]
  4. Borca M. V., Gudmundsdottir I., Fernández-Sainz I. J., Holinka L. G., Risatti G. R.. ( 2008;). Patterns of cellular gene expression in swine macrophages infected with highly virulent classical swine fever virus strain Brescia. . Virus Res 138:, 89–96. [CrossRef][PubMed]
    [Google Scholar]
  5. Brohm C., Steinmann E., Friesland M., Lorenz I. C., Patel A., Penin F., Bartenschlager R., Pietschmann T.. ( 2009;). Characterization of determinants important for hepatitis C virus p7 function in morphogenesis by using trans-complementation. . J Virol 83:, 11682–11693. [CrossRef][PubMed]
    [Google Scholar]
  6. Ciechanover A.. ( 1998;). The ubiquitin–proteasome pathway: on protein death and cell life. . EMBO J 17:, 7151–7160. [CrossRef][PubMed]
    [Google Scholar]
  7. Dong X.-Y., Liu W.-J., Zhao M.-Q., Wang J.-Y., Pei J.-J., Luo Y.-W., Ju C.-M., Chen J.-D.. ( 2013;). Classical swine fever virus triggers RIG-I and MDA5-dependent signaling pathway to IRF-3 and NF-κB activation to promote secretion of interferon and inflammatory cytokines in porcine alveolar macrophages. . Virol J 10:, 286. [CrossRef][PubMed]
    [Google Scholar]
  8. Dreier S., Zimmermann B., Moennig V., Greiser-Wilke I.. ( 2007;). A sequence database allowing automated genotyping of Classical swine fever virus isolates. . J Virol Methods 140:, 95–99. [CrossRef][PubMed]
    [Google Scholar]
  9. Franck N., Le Seyec J., Guguen-Guillouzo C., Erdtmann L.. ( 2005;). Hepatitis C virus NS2 protein is phosphorylated by the protein kinase CK2 and targeted for degradation to the proteasome. . J Virol 79:, 2700–2708. [CrossRef][PubMed]
    [Google Scholar]
  10. Gladue D. P., Zhu J., Holinka L. G., Fernandez-Sainz I., Carrillo C., Prarat M. V., O’Donnell V., Borca M. V.. ( 2010;). Patterns of gene expression in swine macrophages infected with classical swine fever virus detected by microarray. . Virus Res 151:, 10–18. [CrossRef][PubMed]
    [Google Scholar]
  11. Gladue D. P., Holinka L. G., Largo E., Fernandez Sainz I., Carrillo C., O’Donnell V., Baker-Branstetter R., Lu Z., Ambroggio X.. & other authors ( 2012;). Classical swine fever virus p7 protein is a viroporin involved in virulence in swine. . J Virol 86:, 6778–6791. [CrossRef][PubMed]
    [Google Scholar]
  12. Glickman M. H., Ciechanover A.. ( 2002;). The ubiquitin–proteasome proteolytic pathway: destruction for the sake of construction. . Physiol Rev 82:, 373–428.[PubMed]
    [Google Scholar]
  13. Guo H. C., Sun S. Q., Sun D. H., Wei Y. Q., Xu J., Huang M., Liu X. T., Liu Z. X., Luo J. X.. & other authors ( 2013a;). Viroporin activity and membrane topology of classic swine fever virus p7 protein. . Int J Biochem Cell Biol 45:, 1186–1194. [CrossRef][PubMed]
    [Google Scholar]
  14. Guo K.-K., Tang Q.-H., Ning P.-B., Li H.-L., Liu W., Lv Q.-Z., Liang W.-L., Lin Z., Zhang C.-C.. & other authors ( 2013b;). Pilot study on degradation of classical swine fever virus nonstructural 2 protein in cells. . J Anim Vet Adv 12:, 234–241.
    [Google Scholar]
  15. Haqshenas G.. ( 2013;). The p7 protein of hepatitis C virus is degraded via the proteasome-dependent pathway. . Virus Res 176:, 211–215. [CrossRef][PubMed]
    [Google Scholar]
  16. Harada T., Tautz N., Thiel H. J.. ( 2000;). E2-p7 region of the bovine viral diarrhea virus polyprotein: processing and functional studies. . J Virol 74:, 9498–9506. [CrossRef][PubMed]
    [Google Scholar]
  17. He L., Zhang Y. M., Lin Z., Li W. W., Wang J., Li H.-L.. ( 2012;). Classical swine fever virus NS5A protein localizes to endoplasmic reticulum and induces oxidative stress in vascular endothelial cells. . Virus Genes 45:, 274–282. [CrossRef][PubMed]
    [Google Scholar]
  18. Horng T.. ( 2014;). Calcium signaling and mitochondrial destabilization in the triggering of the NLRP3 inflammasome. . Trends Immunol 35:, 253–261. [CrossRef][PubMed]
    [Google Scholar]
  19. Hüsser L., Alves M. P., Ruggli N., Summerfield A.. ( 2011;). Identification of the role of RIG-I, MDA-5 and TLR3 in sensing RNA viruses in porcine epithelial cells using lentivirus-driven RNA interference. . Virus Res 159:, 9–16. [CrossRef][PubMed]
    [Google Scholar]
  20. Ichinohe T., Pang I. K., Iwasaki A.. ( 2010;). Influenza virus activates inflammasomes via its intracellular M2 ion channel. . Nat Immunol 11:, 404–410. [CrossRef][PubMed]
    [Google Scholar]
  21. Ito M., Yanagi Y., Ichinohe T.. ( 2012;). Encephalomyocarditis virus viroporin 2B activates NLRP3 inflammasome. . PLoS Pathog 8:, e1002857. [CrossRef][PubMed]
    [Google Scholar]
  22. Kanneganti T.-D.. ( 2010;). Central roles of NLRs and inflammasomes in viral infection. . Nat Rev Immunol 10:, 688–698. [CrossRef][PubMed]
    [Google Scholar]
  23. Kanneganti T. D., Body-Malapel M., Amer A., Park J. H., Whitfield J., Franchi L., Taraporewala Z. F., Miller D., Patton J. T.. & other authors ( 2006;). Critical role for Cryopyrin/Nalp3 in activation of caspase-1 in response to viral infection and double-stranded RNA. . J Biol Chem 281:, 36560–36568. [CrossRef][PubMed]
    [Google Scholar]
  24. Kato H., Takeuchi O., Sato S., Yoneyama M., Yamamoto M., Matsui K., Uematsu S., Jung A., Kawai T.. & other authors ( 2006;). Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. . Nature 441:, 101–105. [CrossRef][PubMed]
    [Google Scholar]
  25. Kaushik D. K., Gupta M., Kumawat K. L., Basu A.. ( 2012;). NLRP3 inflammasome: key mediator of neuroinflammation in murine Japanese encephalitis. . PLoS ONE 7:, e32270. [CrossRef][PubMed]
    [Google Scholar]
  26. Knoetig S. M., Summerfield A., Spagnuolo-Weaver M., McCullough K. C.. ( 1999;). Immunopathogenesis of classical swine fever: role of monocytic cells. . Immunology 97:, 359–366. [CrossRef][PubMed]
    [Google Scholar]
  27. Lamp B., Riedel C., Roman-Sosa G., Heimann M., Jacobi S., Becher P., Thiel H.-J., Rümenapf T.. ( 2011;). Biosynthesis of classical swine fever virus nonstructural proteins. . J Virol 85:, 3607–3620. [CrossRef][PubMed]
    [Google Scholar]
  28. Largo E., Gladue D. P., Huarte N., Borca M. V., Nieva J. L.. ( 2014;). Pore-forming activity of pestivirus p7 in a minimal model system supports genus-specific viroporin function. . Antiviral Res 101:, 30–36. [CrossRef][PubMed]
    [Google Scholar]
  29. Lee G.-S., Subramanian N., Kim A. I., Aksentijevich I., Goldbach-Mansky R., Sacks D. B., Germain R. N., Kastner D. L., Chae J. J.. ( 2012;). The calcium-sensing receptor regulates the NLRP3 inflammasome through Ca2+ and cAMP. . Nature 492:, 123–127. [CrossRef][PubMed]
    [Google Scholar]
  30. Livak K. J., Schmittgen T. D.. ( 2001;). Analysis of relative gene expression data using real-time quantitative PCR and the 2–ΔΔCT method. . Methods 25:, 402–408. [CrossRef][PubMed]
    [Google Scholar]
  31. Loo Y.-M., Fornek J., Crochet N., Bajwa G., Perwitasari O., Martinez-Sobrido L., Akira S., Gill M. A., García-Sastre A.. & other authors ( 2008;). Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity. . J Virol 82:, 335–345. [CrossRef][PubMed]
    [Google Scholar]
  32. Murakami T., Ockinger J., Yu J., Byles V., McColl A., Hofer A. M., Horng T.. ( 2012;). Critical role for calcium mobilization in activation of the NLRP3 inflammasome. . Proc Natl Acad Sci U S A 109:, 11282–11287. [CrossRef][PubMed]
    [Google Scholar]
  33. Negash A. A., Ramos H. J., Crochet N., Lau D. T., Doehle B., Papic N., Delker D. A., Jo J., Bertoletti A.. & other authors ( 2013;). IL-1β production through the NLRP3 inflammasome by hepatic macrophages links hepatitis C virus infection with liver inflammation and disease. . PLoS Pathog 9:, e1003330. [CrossRef][PubMed]
    [Google Scholar]
  34. Piccioli P., Rubartelli A.. ( 2013;). The secretion of IL-1β and options for release. . Semin Immunol 25:, 425–429. [CrossRef][PubMed]
    [Google Scholar]
  35. Poeck H., Bscheider M., Gross O., Finger K., Roth S., Rebsamen M., Hannesschläger N., Schlee M., Rothenfusser S.. & other authors ( 2010;). Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1 beta production. . Nat Immunol 11:, 63–69. [CrossRef][PubMed]
    [Google Scholar]
  36. Ramos H. J., Lanteri M. C., Blahnik G., Negash A., Suthar M. S., Brassil M. M., Sodhi K., Treuting P. M., Busch M. P.. & other authors ( 2012;). IL-1β signaling promotes CNS-intrinsic immune control of West Nile virus infection. . PLoS Pathog 8:, e1003039. [CrossRef][PubMed]
    [Google Scholar]
  37. Schroder K., Tschopp J.. ( 2010;). The inflammasomes. . Cell 140:, 821–832. [CrossRef][PubMed]
    [Google Scholar]
  38. Shrivastava S., Mukherjee A., Ray R., Ray R. B.. ( 2013;). Hepatitis C virus induces interleukin-1β (IL-1β)/IL-18 in circulatory and resident liver macrophages. . J Virol 87:, 12284–12290. [CrossRef][PubMed]
    [Google Scholar]
  39. Takeuchi O., Akira S.. ( 2008;). MDA5/RIG-I and virus recognition. . Curr Opin Immunol 20:, 17–22. [CrossRef][PubMed]
    [Google Scholar]
  40. Thiel H. J., Stark R., Weiland E., Rümenapf T., Meyers G.. ( 1991;). Hog cholera virus: molecular composition of virions from a pestivirus. . J Virol 65:, 4705–4712.[PubMed]
    [Google Scholar]
  41. van de Veerdonk F. L., Netea M. G., Dinarello C. A., Joosten L. A.. ( 2011;). Inflammasome activation and IL-1β and IL-18 processing during infection. . Trends Immunol 32:, 110–116. [CrossRef][PubMed]
    [Google Scholar]
  42. Wang K.. ( 2013;). Viroporin activates inflammasome. . J. Appl. Virol. 2:, 1–5.
    [Google Scholar]
  43. Weingartl H. M., Sabara M., Pasick J., van Moorlehem E., Babiuk L.. ( 2002;). Continuous porcine cell lines developed from alveolar macrophages: partial characterization and virus susceptibility. . J Virol Methods 104:, 203–216. [CrossRef][PubMed]
    [Google Scholar]
  44. Zaffuto K. M., Piccone M. E., Burrage T. G., Balinsky C. A., Risatti G. R., Borca M. V., Holinka L. G., Rock D. L., Afonso C. L.. ( 2007;). Classical swine fever virus inhibits nitric oxide production in infected macrophages. . J Gen Virol 88:, 3007–3012. [CrossRef][PubMed]
    [Google Scholar]
  45. Zhang K., Hou Q., Zhong Z., Li X., Chen H., Li W., Wen J., Wang L., Liu W., Zhong F.. ( 2013;). Porcine reproductive and respiratory syndrome virus activates inflammasomes of porcine alveolar macrophages via its small envelope protein E. . Virology 442:, 156–162. [CrossRef][PubMed]
    [Google Scholar]
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