title: Transmissible gastroenteritis virus infection induces apoptosis through FasL- and mitochondria-mediated pathways.
abstract: Transmissible gastroenteritis virus (TGEV) has been reported to induce apoptosis in swine testis (ST) cells. However, the mechanisms underlying TGEV-induced apoptosis are still unclear. In this study we observed that TGEV infection induced apoptosis in porcine kidney (PK-15) cells in a time- and dose-dependent manner. TGEV infection up-regulated FasL, activated FasL-mediated apoptotic pathway, leading to activation of caspase-8 and cleavage of Bid. In addition, TGEV infection down-regulated Bcl-2, up-regulated Bax expression, promoted translocation of Bax to mitochondria, activated mitochondria-mediated apoptotic pathway, which in turn caused the release of cytochrome c and the activation of caspase-9. Both extrinsic and intrinsic pathways activated downstream effector caspase-3, followed by the cleavage of PARP, resulting in cell apoptosis. Moreover, TGEV infection did not induce significant DNA fragmentation in ammonium chloride (NH(4)Cl) pretreated PK-15 cells or cells infected with UV-inactivated TGEV. In turn, block of caspases activation also did not affect TGEV replication. Taken together, this study demonstrates that TGEV-induced apoptosis is dependent on viral replication in PK-15 cells and occurs through activation of FasL- and mitochondria-mediated apoptotic pathways.
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.forename: Xingang
authors.initials: X
authors.lastname: Xu
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.forename: Zhaocai
authors.initials: Z
authors.lastname: Li
authors.forename: Kuan
authors.initials: K
authors.lastname: Zhang
authors.forename: Guangda
authors.initials: G
authors.lastname: Chen
authors.forename: Gaoshui
authors.initials: G
authors.lastname: Yu
authors.forename: Zhisheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Dewen
authors.initials: D
authors.lastname: Tong
mesh_terms: D000818:Animals; D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D002460:Cell Line; D053222:Fas Ligand Protein / Q000378:metabolism*; D005761:Gastroenteritis, Transmissible, of Swine / Q000378:metabolism* / Q000821:virology*; D008928:Mitochondria / Q000378:metabolism*; D013552:Swine; D005760:Transmissible gastroenteritis virus / Q000502:physiology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; D053222:Fas Ligand Protein; D051028:bcl-2-Associated X Protein; D019014:fas Receptor