title: Activation of c-Jun NH(2)-terminal kinase is required for porcine reproductive and respiratory syndrome virus-induced apoptosis but not for virus replication.
abstract: Apoptosis of host cells plays a critical role in pathogenesis of virus infection. MAPK kinases especially stress-activated protein kinases c-Jun NH(2)-terminal kinase (SAPK/JNK) and p38 are often involved in virus-mediated apoptosis. It has been shown that porcine reproductive and respiratory syndrome virus (PRRSV) infection resulted in apoptosis of the host cells both in vitro and in vivo. The current investigation was initiated to determine whether stress-activated protein kinases JNK and p38 play a role in apoptosis induction by PRRSV infection. We examined phosphorylation of JNK and p38, and found that JNK but not p38 was activated in response to PRRSV infection. We then examined effects of this kinase on apoptosis induction and virus replication by using specific inhibitor. We found that JNK inhibition by its inhibitor SP600125 led to the abolishment of PRRSV-mediated apoptosis, but did not suppress virus replication. Further studies demonstrated that ROS generation was involved in JNK activation, and Bcl-2 family anti-apoptotic proteins Mcl-1 and Bcl-xl were downstream targets of JNK to mediate apoptosis. We conclude that activation of JNK signaling pathway is essential for PRRSV-mediated apoptosis but not for virus replication.
authors.affiliation: Division of Nutrition and Health, College of Food Science and Nutritional Engineering, China Agricultural University, No. 17 Qinghua East Road, Haidian District, Beijing 100083, China.
authors.forename: Shutao
authors.initials: S
authors.lastname: Yin
authors.forename: Yazhen
authors.initials: Y
authors.lastname: Huo
authors.forename: Yinhui
authors.initials: Y
authors.lastname: Dong
authors.forename: Lihong
authors.initials: L
authors.lastname: Fan
authors.forename: Hanchun
authors.initials: H
authors.lastname: Yang
authors.forename: Leyuan
authors.initials: L
authors.lastname: Wang
authors.forename: Yibao
authors.initials: Y
authors.lastname: Ning
authors.forename: Hongbo
authors.initials: H
authors.lastname: Hu
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002522:Chlorocebus aethiops; D054884:Host-Pathogen Interactions; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D019316:Porcine respiratory and reproductive syndrome virus / Q000472:pathogenicity* / Q000502:physiology; D015533:Transcriptional Activation; D014779:Virus Replication; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases