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.
Virus Res. 2012 Jun;166(1-2):103-8. doi: 10.1016/j.virusres.2012.03.010. Epub 2012 Mar 27.
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.
宿主细胞的凋亡在病毒感染的发病机制中起着关键作用。丝裂原活化蛋白激酶（MAPK）激酶，特别是应激激活蛋白激酶 c-Jun NH（2）-末端激酶（SAPK/JNK）和 p38，通常参与病毒介导的细胞凋亡。已经表明，猪繁殖与呼吸综合征病毒（PRRSV）感染导致体外和体内宿主细胞凋亡。目前的研究旨在确定应激激活蛋白激酶 JNK 和 p38是否在 PRRSV 感染诱导的细胞凋亡中发挥作用。我们检测了 JNK 和 p38 的磷酸化，发现 JNK 而不是 p38 在 PRRSV 感染后被激活。然后，我们通过使用特定抑制剂来检查该激酶对细胞凋亡诱导和病毒复制的影响。我们发现，JNK 抑制剂 SP600125 的抑制导致 PRRSV 介导的细胞凋亡被废除，但不抑制病毒复制。进一步的研究表明，ROS 的产生参与了 JNK 的激活，并且 Bcl-2 家族抗凋亡蛋白 Mcl-1 和 Bcl-xl 是 JNK 的下游靶标，介导细胞凋亡。我们得出结论，JNK 信号通路的激活对于 PRRSV 介导的凋亡是必需的，但对于病毒复制不是必需的。
