title: Transmissible gastroenteritis virus infection induces cell apoptosis via activation of p53 signalling.
abstract: Transmissible gastroenteritis virus (TGEV) infection induced apoptosis in several cell lines in vitro. Our previous studies demonstrated that TGEV could activate FasL- and mitochondria-mediated pathways to induce apoptosis in PK-15 cells. In this study, we investigated the regulation of p53 and p38 mitogen-activated protein kinases (MAPK) signalling pathways in the interaction of TGEV with host cells. We observed that TGEV infection decreased p300/CBP, downregulated MDM2 and promoted p53 phosphorylation at serines 15, 20 and 46, resulting in accumulation and activation of p53 in PK-15 cells. TGEV infection induced the transient activation of p38 MAPK in the early phase of inoculation and constant activation in the later phase of infection. However, UV-irradiated TGEV did not promote the activation of p53 and p38 MAPK in the later phase, whereas it only triggered the transient activation of p38 MAPK in the early phase. Blocking of p53 activation significantly inhibited the occurrence of apoptosis through suppressing the TGEV-induced FasL expression, Bcl-2 reduction, Bax and cytochrome c redistribution, while inhibition of p38 activity moderately blocked apoptosis induction and partly attenuated the accumulation and activation of p53. However, inhibition of p38 and p53 activity had no significant effects on viral gene transcription at 12 and 24 h post-infection. Taken together, these results demonstrated that TGEV infection promoted the activation of p38 MAPK and p53 signalling, and p53 signalling might play a dominant role in the regulation of cell apoptosis. These findings provide new insights into the function of p53 and p38 MAPK in the interaction of TGEV with host cells.
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, P.R. China.
authors.forename: Zhaocai
authors.initials: Z
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, P.R. China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Dai
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, P.R. China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Du
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, P.R. China.
authors.forename: Xingang
authors.initials: X
authors.lastname: Xu
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, P.R. China.
authors.forename: Dewen
authors.initials: D
authors.lastname: Tong
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D054884:Host-Pathogen Interactions; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D013552:Swine; D005760:Transmissible gastroenteritis virus / Q000472:pathogenicity*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53; D012694:Serine; D048051:p38 Mitogen-Activated Protein Kinases