1887

Abstract

Classical swine fever virus (CSFV) causes severe disease in pigs associated with leukopenia, haemorrhage and fever. We show that CSFV infection protects endothelial cells from apoptosis induced by the dsRNA mimic, pIpC, but not from other apoptotic stimuli, FasL or staurosporine. CSFV infection inhibits pIpC-induced caspase activation, mitochondrial membrane potential loss and cytochrome release as well as the pro-apoptotic effects of truncated Bid (tBid) overexpression. The CSFV proteins N and E both contribute to CSFV inhibition of apoptosis. We conclude that CSFV infection can inhibit apoptotic signalling at multiple levels, including at the caspase-8 and the mitochondrial checkpoints. By supporting viral replication, endothelial cells may promote CSFV pathogenesis.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.016576-0
2010-04-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/91/4/1038.html?itemId=/content/journal/jgv/10.1099/vir.0.016576-0&mimeType=html&fmt=ahah

References

  1. Andersen, J., VanScoy, S., Cheng, T. F., Gomez, D. & Reich, N. C.(2007). IRF-3-dependent and augmented target genes during viral infection. Genes Immun 9, 168–175. [Google Scholar]
  2. Bauhofer, O., Summerfield, A., Sakoda, Y., Tratschin, J. D., Hofmann, M. A. & Ruggli, N.(2007). Classical swine fever virus Npro interacts with interferon regulatory factor 3 and induces its proteasomal degradation. J Virol 81, 3087–3096.[CrossRef] [Google Scholar]
  3. Benedict, C. A., Norris, P. S. & Ware, C. F.(2002). To kill or be killed: viral evasion of apoptosis. Nat Immunol 3, 1013–1018.[CrossRef] [Google Scholar]
  4. Bensaude, E., Turner, J. L., Wakeley, P. R., Sweetman, D. A., Pardieu, C., Drew, T. W., Wileman, T. & Powell, P. P.(2004). Classical swine fever virus induces proinflammatory cytokines and tissue factor expression and inhibits apoptosis and interferon synthesis during the establishment of long-term infection of porcine vascular endothelial cells. J Gen Virol 85, 1029–1037.[CrossRef] [Google Scholar]
  5. Campos, E., Revilla, C., Chamorro, S., Alvarez, B., Ezquerra, A., Dominguez, J. & Alonso, F.(2004).In vitro effect of classical swine fever virus on a porcine aortic endothelial cell line. Vet Res 35, 625–633.[CrossRef] [Google Scholar]
  6. Carrillo, A., Chamorro, S., Rodriguez-Gago, M., Alvarez, B., Molina, M. J., Rodriguez-Barbosa, J. I., Sanchez, A., Ramirez, P., Munoz, A. & other authors(2002). Isolation and characterization of immortalized porcine aortic endothelial cell lines. Vet Immunol Immunopathol 89, 91–98.[CrossRef] [Google Scholar]
  7. Choi, C., Hwang, K. K. & Chae, C.(2004). Classical swine fever virus induces tumor necrosis factor-α and lymphocyte apoptosis. Arch Virol 149, 875–889.[CrossRef] [Google Scholar]
  8. Cohen, G. M.(1997). Caspases: the executioners of apoptosis. Biochem J 326, 1–16. [Google Scholar]
  9. Dinger, M. E., Mercer, T. R. & Mattick, J. S.(2008). RNAs as extracellular signaling molecules. J Mol Endocrinol 40, 151–159.[CrossRef] [Google Scholar]
  10. Doukas, J., Cutler, A. H. & Mordes, J. P.(1994). Polyinosinic : polycytidylic acid is a potent activator of endothelial cells. Am J Pathol 145, 137–147. [Google Scholar]
  11. Edwards, S. & Sands, J. J.(1990). Antigenic comparisons of hog cholera virus isolates from Europe, America and Asia using monoclonal antibodies. Dtsch Tierarztl Wochenschr 97, 79–81. [Google Scholar]
  12. Galluzzi, L., Brenner, C., Morselli, E., Touat, Z. & Kroemer, G.(2008). Viral control of mitochondrial apoptosis. PLoS Pathog 4, e1000018[CrossRef] [Google Scholar]
  13. Ganges, L., Nunez, J. I., Sobrino, F., Borrego, B., Fernandez-Borges, N., Frias-Lepoureau, M. T. & Rodriguez, F.(2008). Recent advances in the development of recombinant vaccines against classical swine fever virus: cellular responses also play a role in protection. Vet J 177, 169–177.[CrossRef] [Google Scholar]
  14. Garcia, M. A., Meurs, E. F. & Esteban, M.(2007). The dsRNA protein kinase PKR: virus and cell control. Biochimie 89, 799–811.[CrossRef] [Google Scholar]
  15. Heibein, J. A., Barry, M., Motyka, B. & Bleackley, R. C.(1999). Granzyme B-induced loss of mitochondrial inner membrane potential (ΔΨm) and cytochrome c release are caspase independent. J Immunol 163, 4683–4693. [Google Scholar]
  16. Iordanov, M. S., Kirsch, J. D., Ryabinina, O. P., Wong, J., Spitz, P. N., Korcheva, V. B., Thorburn, A. & Magun, B. E.(2005a). Recruitment of TRADD, FADD, and caspase 8 to double-stranded RNA-triggered death inducing signaling complexes (dsRNA-DISCs). Apoptosis 10, 167–176.[CrossRef] [Google Scholar]
  17. Iordanov, M. S., Ryabinina, O. P., Schneider, P. & Magun, B. E.(2005b). Two mechanisms of caspase 9 processing in double-stranded RNA- and virus-triggered apoptosis. Apoptosis 10, 153–166.[CrossRef] [Google Scholar]
  18. Iqbal, M., Poole, E., Goodbourn, S. & McCauley, J. W.(2004). Role for bovine viral diarrhea virus Erns glycoprotein in the control of activation of beta interferon by double-stranded RNA. J Virol 78, 136–145.[CrossRef] [Google Scholar]
  19. Kaiser, W. J., Kaufman, J. L. & Offermann, M. K.(2004). IFN-α sensitizes human umbilical vein endothelial cells to apoptosis induced by double-stranded RNA. J Immunol 172, 1699–1710.[CrossRef] [Google Scholar]
  20. La Rocca, S. A., Herbert, R. J., Crooke, H., Drew, T. W., Wileman, T. E. & Powell, P. P.(2005). Loss of interferon regulatory factor 3 in cells infected with classical swine fever virus involves the N-terminal protease, Npro. J Virol 79, 7239–7247.[CrossRef] [Google Scholar]
  21. Le Potier, M., Mesplede, A. & Vannier, P.(2006). Classical swine fever and other pestiviruses. In Diseases of Swine, 9th edn, pp. 309–322. Edited by B. E. Straw, J. J. Zimmerman, S. D'Allaire & D. J. Taylor. Ames, Iowa: Blackwell.
  22. Li, K., Foy, E., Ferreon, J. C., Nakamura, M., Ferreon, A. C. M., Ikeda, M., Ray, S. C., Gale, M. & Lemon, S. M.(2005). Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIF. Proc Natl Acad Sci U S A 102, 2992–2997.[CrossRef] [Google Scholar]
  23. Magkouras, I., Matzener, P., Rumenapf, T., Peterhans, E. & Schweizer, M.(2008). RNase-dependent inhibition of extracellular, but not intracellular, dsRNA-induced interferon synthesis by Erns of pestiviruses. J Gen Virol 89, 2501–2506.[CrossRef] [Google Scholar]
  24. Majde, J. A., Guha-Thakurta, N., Chen, Z., Bredow, S. & Krueger, J. M.(1998). Spontaneous release of stable viral double-stranded RNA into the extracellular medium by influenza virus-infected MDCK epithelial cells: implications for the viral acute phase response. Arch Virol 143, 2371–2380.[CrossRef] [Google Scholar]
  25. Matzener, P., Magkouras, I., Rumenapf, T., Peterhans, E. & Schweizer, M.(2009). The viral RNase Erns prevents IFN type-I triggering by pestiviral single- and double-stranded RNAs. Virus Res 140, 15–23.[CrossRef] [Google Scholar]
  26. Nagata, S.(1999). FAS ligand-induced apoptosis. Annu Rev Genet 33, 29–55.[CrossRef] [Google Scholar]
  27. Paton, D. J. & Greiser-Wilke, I.(2003). Classical swine fever – an update. Res Vet Sci 75, 169–178.[CrossRef] [Google Scholar]
  28. Rintahaka, J., Wiik, D., Kovanen, P. E., Alenius, H. & Matikainen, S.(2008). Cytosolic antiviral RNA recognition pathway activates caspases 1 and 3. J Immunol 180, 1749–1757.[CrossRef] [Google Scholar]
  29. Rodriguez, J. & Lazebnik, Y.(1999). Caspase-9 and APAF-1 form an active holoenzyme. Genes Dev 13, 3179–3184.[CrossRef] [Google Scholar]
  30. Ruggli, N., Tratschin, J. D., Schweizer, M., McCullough, K. C., Hofmann, M. A. & Summerfield, A.(2003). Classical swine fever virus interferes with cellular antiviral defense: evidence for a novel function of Npro. J Virol 77, 7645–7654.[CrossRef] [Google Scholar]
  31. Ruggli, N., Bird, B. H., Liu, L., Bauhofer, O., Tratschin, J. D. & Hofmann, M. A.(2005). Npro of classical swine fever virus is an antagonist of double-stranded RNA-mediated apoptosis and IFN-α/β induction. Virology 340, 265–276.[CrossRef] [Google Scholar]
  32. Rumenapf, T., Stark, R., Heimann, M. & Thiel, H.-J.(1998). N-terminal protease of pestiviruses: identification of putative catalytic residues by site-directed mutagenesis. J Virol 72, 2544–2547. [Google Scholar]
  33. Salaun, B., Coste, I., Rissoan, M. C., Lebecque, S. J. & Renno, T.(2006). TLR3 can directly trigger apoptosis in human cancer cells. J Immunol 176, 4894–4901.[CrossRef] [Google Scholar]
  34. Sanchez-Cordon, P. J., Romanini, S., Salguero, F. J., Nunez, A., Bautista, M. J., Jover, A. & Gomez-Villamos, J. C.(2002). Apoptosis of thymocytes related to cytokine expression in experimental classical swine fever. J Comp Pathol 127, 239–248.[CrossRef] [Google Scholar]
  35. Sato, M., Mikami, O., Kobayashi, M. & Nakajima, Y.(2000). Apoptosis in the lymphatic organs of piglets inoculated with classical swine fever virus. Vet Microbiol 75, 1–9.[CrossRef] [Google Scholar]
  36. Seago, J., Hilton, L., Reid, E., Doceul, V., Jeyatheesan, J., Moganeradj, K., McCauley, J., Charleston, B. & Goodbourn, S.(2007). The Npro product of classical swine fever virus and bovine viral diarrhea virus uses a conserved mechanism to target interferon regulatory factor-3. J Gen Virol 88, 3002–3006.[CrossRef] [Google Scholar]
  37. Summerfield, A., Knoetig, S. M., Tschudin, R. & McCullough, K. C.(2000). Pathogenesis of granulocytopenia and bone marrow atrophy during classical swine fever involves apoptosis and necrosis of uninfected cells. Virology 272, 50–60.[CrossRef] [Google Scholar]
  38. Summerfield, A., Zingle, K., Inumaru, S. & McCullough, K. C.(2001). Induction of apoptosis in bone marrow neutrophil-lineage cells by classical swine fever virus. J Gen Virol 82, 1309–1318. [Google Scholar]
  39. Takahashi, K., Kawai, T., Kumar, H., Sato, S., Yonehara, S. & Akira, S.(2006). Roles of caspase-8 and caspase-10 in innate immune responses to double-stranded RNA. J Immunol 176, 4520–4524.[CrossRef] [Google Scholar]
  40. von Freyburg, M., Ege, A., Saalmuller, A. & Meyers, G.(2004). Comparison of the effects of RNase-negative and wild-type classical swine fever virus on peripheral blood cells of infected pigs. J Gen Virol 85, 1899–1908.[CrossRef] [Google Scholar]
  41. Youle, R. J. & Strasser, A.(2008). The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol 9, 47–59.[CrossRef] [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.016576-0
Loading
/content/journal/jgv/10.1099/vir.0.016576-0
Loading

Data & Media loading...

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