Critical role of cytochrome c1 and its cleavage in porcine reproductive and respiratory syndrome virus nonstructural protein 4-induced cell apoptosis via interaction with nsp4  

作　　者：ZHANG Feng GAO Peng GE Xin-na ZHOU Lei GUO Xin YANG Han-chun 

机构地区：[1]Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, State Key Laboratory ofAgrobiotechnology, China Agricultural University, Beijing 100193, P.R.China

出　　处：《Journal of Integrative Agriculture》2017年第11期2573-2585,共13页农业科学学报（英文版）

基　　金：supported by the National 973 Program of China(2014CB542700);the National Natural Science Foundation of China(31330077,31540004);the earmarked fund for China Agriculture Research System(CARS-36)

摘　　要：Porcine reproductive and respiratory syndrome virus.（PRRSV） actively induces cell apoptosis both in vitro and in vivo, which can contribute critically to viral pathogenesis. Previous studies have shown that the PRRSV nonstructural protein 4 （nsp4） is an important mediator of this process, but the underlying molecular details remain poorly understood. In this study, we found that the PRRSV nsp4 interacted with the mitochondrial inner membrane protein cytochrome cl （cyto.cl） and induced its proteolytic cleavage. Interestingly, the cleaved N-terminal fragment of cyto.cl was found to exert apoptotic activity, which could cause mitochondrial fragmentation, resulting in apoptotic cell death. And RNA interference （RNAi） silencing experiments further confirmed the crucial role which cyto.cl played in nsp4- and PRRSV-induced cell apoptosis. Thus, our data provide an important piece of mechanistic clues for PRRSV-induced cell apoptosis and also elucidate a novel mechanism for the 3C-like proteases in this finding.Porcine reproductive and respiratory syndrome virus.（PRRSV） actively induces cell apoptosis both in vitro and in vivo, which can contribute critically to viral pathogenesis. Previous studies have shown that the PRRSV nonstructural protein 4 （nsp4） is an important mediator of this process, but the underlying molecular details remain poorly understood. In this study, we found that the PRRSV nsp4 interacted with the mitochondrial inner membrane protein cytochrome cl （cyto.cl） and induced its proteolytic cleavage. Interestingly, the cleaved N-terminal fragment of cyto.cl was found to exert apoptotic activity, which could cause mitochondrial fragmentation, resulting in apoptotic cell death. And RNA interference （RNAi） silencing experiments further confirmed the crucial role which cyto.cl played in nsp4- and PRRSV-induced cell apoptosis. Thus, our data provide an important piece of mechanistic clues for PRRSV-induced cell apoptosis and also elucidate a novel mechanism for the 3C-like proteases in this finding.

关 键 词：PRRSV nonstructural protein4 （nsp4） cytochrome cl （cyto.cl） INTERACTION CLEAVAGE apoptosis 

分 类 号：S852.651[农业科学—基础兽医学]