Animal Virology Laboratory, School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, Republic of Korea.
Animal Virology Laboratory, School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, Republic of Korea.
Virology. 2014 Jul;460-461:180-93. doi: 10.1016/j.virol.2014.04.040. Epub 2014 Jun 5.
The present study sought to investigate whether porcine epidemic diarrhea virus (PEDV) induces apoptosis and to elucidate the mechanisms associated with apoptotic cell death after PEDV infection. PEDV-infected cells showed evidence of apoptosis in vitro and in vivo. However, experimental data indicated that the caspase cascade is not involved in PEDV-induced apoptotic cell death. Interestingly, mitochondrial apoptosis-inducing factor (AIF) was found to translocate to the nucleus during PEDV infection, and AIF relocalization was completely abrogated by the presence of cyclosporin A (CsA), an inhibitor of cyclophilin D (CypD) that is an essential component of the mitochondrial permeabilization transition pore (mPTP) complex. CsA treatment resulted in significant inhibition of PEDV-triggered apoptosis and suppressed PEDV replication. Furthermore, direct inhibition of AIF strongly impaired PEDV infection and virus-induced apoptosis. Altogether, our results indicate that a caspase-independent mitochondrial AIF-mediated pathway plays a central role in PEDV-induced apoptosis to facilitate viral replication and pathogenesis.
本研究旨在探讨猪流行性腹泻病毒（PEDV）是否诱导细胞凋亡，并阐明 PEDV 感染后与凋亡细胞死亡相关的机制。PEDV 感染的细胞在体外和体内均显示出凋亡的证据。然而，实验数据表明，半胱天冬酶级联反应不参与 PEDV 诱导的细胞凋亡。有趣的是，在线粒体凋亡诱导因子（AIF）在 PEDV 感染过程中被发现向核内易位，并且环孢菌素 A（CsA）完全阻断了 AIF 的重定位，环孢菌素 A 是细胞色素 P450 家族 D（CypD）的抑制剂，是线粒体通透转换孔（mPTP）复合物的必需组成部分。CsA 处理导致 PEDV 触发的凋亡显著抑制，并抑制 PEDV 复制。此外，AIF 的直接抑制强烈削弱了 PEDV 感染和病毒诱导的凋亡。总的来说，我们的结果表明，一种不依赖半胱天冬酶的线粒体 AIF 介导的途径在 PEDV 诱导的凋亡中发挥核心作用，以促进病毒复制和发病机制。
