Analysis of in vitro apoptosis induced by virulent Korean isolate of classical swine fever virus in peripheral blood B cell line

  • Kim, Seon-Mi (Animal, Plant and Fisheries Quarantine and Inspection Agency) ;
  • Lim, Seong-In (Animal, Plant and Fisheries Quarantine and Inspection Agency) ;
  • Song, Jae-Young (Animal, Plant and Fisheries Quarantine and Inspection Agency) ;
  • Hyun, Bang-Hun (Animal, Plant and Fisheries Quarantine and Inspection Agency)
  • Received : 2012.04.24
  • Accepted : 2012.11.14
  • Published : 2012.12.31


Classical swine fever (CSF) is a highly contagious disease among swine that has an important economic impact on worldwide. One clinical symptom of CSF is leukopenia, in particular lymphopenia, which is a characteristic event that occurs early in the course of CSF. Though lymphopenia associated with apoptosis, the pathogenic mechanism underlying the lymphopenia has not been well studied. To understand these mechanisms, we investigated the response of porcine B cell lines to infection with SW03, virulent strain isolated from swine tissue in Korea. This study demonstrated that SW03-infected L35 cell were induced apoptosis through the detection of activated caspase-3. In addition, SW03 infection leaded to alterations in pro-apoptotic, Bax, and anti-apoptotic, Bcl-xL proteins of Bcl-2 family. Our results would suggest that SW03-infected L35 cells induced apoptosis via intrinsic mitochondrial pathway.


  1. Bonenfant C, Vallee I, Sun J, Brossay A, Thibault G, Guillaumin JM, Lebranchu Y, Bardos P, Butler JE, Watier H. Analysis of human CD4 T lymphocyte proliferation induced by porcine lymphoblastoid B cell lines. Xenotransplantation 2003, 10, 107-119.
  2. Cha SH, Choi EJ, Park JH, Yoon SR, Kwon JH, Yoon KJ, Song JY. Phylogenetic characterization of classical swine fever viruses isolated in Korea between 1988 and 2003. Virus Res 2007, 126, 256-261.
  3. Chowdhury I, Tharakan B, Bhat GK. Caspases - an update. Comp Biochem Physiol B Biochem Mol Biol 2008, 151, 10-27.
  4. Cohen GM. Caspases: the executioners of apoptosis. Biochem J 1997, 326 (Pt 1), 1-16.
  5. Deng L, Adachi T, Kitayama K, Bungyoku Y, Kitazawa S, Ishido S, Shoji I, Hotta H. Hepatitis C virus infection induces apoptosis through a Bax-triggered, mitochondrionmediated, caspase 3-dependent pathway. J Virol 2008, 82, 10375-10385.
  6. Ding L, Xu X, Huang Y, Li Z, Zhang K, Chen G, Yu G, Wang Z, Li W, Tong D. Transmissible gastroenteritis virus infection induces apoptosis through FasL- and mitochondria-mediated pathways. Vet Microbiol 2012, 158, 12-22.
  7. Galluzzi L, Joza N, Tasdemir E, Maiuri MC, Hengartner M, Abrams JM, Tavernarakis N, Penninger J, Madeo F, Kroemer G. No death without life: vital functions of apoptotic effectors. Cell Death Differ 2008, 15, 1113-1123.
  8. Jamin A, Gorin S, Cariolet R, Le Potier MF, Kuntz- Simon G. Classical swine fever virus induces activation of plasmacytoid and conventional dendritic cells in tonsil, blood, and spleen of infected pigs. Vet Res 2008, 39, 7.
  9. Johns HL, Bensaude E, La Rocca SA, Seago J, Charleston B, Steinbach F, Drew TW, Crooke H, Everett H. Classical swine fever virus infection protects aortic endothelial cells from pIpC-mediated apoptosis. J Gen Virol 2010, 91, 1038-1046.
  10. Jungi TW, Schweizer M, Perler L, Peterhans E. Supernatants of virus-infected macrophages prime uninfected macrophages for lipopolysaccharide-induced apoptosis by both an interferon-dependent and an independent mechanism. Pathobiology 1999, 67, 294-297.
  11. Karalyan Z, Zakaryan H, Arzumanyan H, Sargsyan K, Voskanyan H, Hakobyan L, Abroyan L, Avetisyan A, Karalova E. Pathology of porcine peripheral white blood cells during infection with African swine fever virus. BMC Vet Res 2012, 8, 18.
  12. Koga R, Ohno S, Ikegame S, Yanagi Y. Measles virusinduced immunosuppression in SLAM knock-in mice. J Virol 2010, 84, 5360-5367.
  13. Lee WC, Wang CS, Chien MS. Virus antigen expression and alterations in peripheral blood mononuclear cell subpopulations after classical swine fever virus infection. Vet Microbiol 1999, 67, 17-29.
  14. Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 1997, 91, 479-489.
  15. Luo X, Budihardjo I, Zou H, Slaughter C, Wang X. Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors. Cell 1998, 94, 481-490.
  16. Page GR, Wang FI, Hahn EC. Interaction of pseudorabies virus with porcine peripheral blood lymphocytes. J Leukoc Biol 1992, 52, 441-448.
  17. Pillet S, von Messling V. Canine distemper virus selectively inhibits apoptosis progression in infected immune cells. J Virol 2009, 83, 6279-6287.
  18. Sammicheli S, Dang VP, Ruffin N, Pham HT, Lantto R, Vivar N, Chiodi F, Rethi B. IL-7 promotes CD95-induced apoptosis in B cells via the IFN-${\gamma}$/STAT1 pathway. PLoS ONE 2011, 6, e28629.
  19. Sanchez-Cordon PJ, Romanini S, Salguero FJ, Nunez A, Bautista MJ, Jover A, Gomez-Villamos JC. Apoptosis of thymocytes related to cytokine expression in experimental classical swine fever. J Comp Pathol 2002, 127, 239-248.
  20. Sato M, Mikami O, Kobayashi M, Nakajima Y. Apoptosis in the lymphatic organs of piglets inoculated with classical swine fever virus. Vet Microbiol 2000, 75, 1-9.
  21. Schobesberger M, Summerfield A, Doherr MG, Zurbriggen A, Griot C. Canine distemper virus-induced depletion of uninfected lymphocytes is associated with apoptosis. Vet Immunol Immunopathol 2005, 104, 33-44.
  22. Shi Z, Sun J, Guo H, Tu C. Genomic expression profiling of peripheral blood leukocytes of pigs infected with highly virulent classical swine fever virus strain Shimen. J Gen Virol 2009, 90 (Pt 7), 1670-1680.
  23. Summerfield A, Knotig SM, McCullough KC. Lymphocyte apoptosis during classical swine fever: implication of activation-induced cell death. J Virol 1998, 72, 1853-1861.
  24. Susa M, König M, Saalmüller A, Reddehase MJ, Thiel HJ. Pathogenesis of classical swine fever: B-lymphocyte deficiency caused by hog cholera virus. J Virol 1992, 66, 1171-1175.
  25. Uiprasertkul M, Kitphati R, Puthavathana P, Kriwong R, Kongchanagul A, Ungchusak K, Angkasekwinai S, Chokephaibulkit K, Srisook K, Vanprapar N, Auewarakul P. Apoptosis and pathogenesis of avian influenza A (H5N1) virus in humans. Emerg Infect Dis 2007, 13, 708-712.
  26. von Freyburg M, Ege A, Saalmüller A, Meyers G. Comparison of the effects of RNase-negative and wild-type classical swine fever virus on peripheral blood cells of infected pigs. J Gen Virol 2004, 85 (Pt 7), 1899-1908.