猪流行性腹泻病毒通过病毒蛋白酶激活Caspase-3诱导细胞凋亡

冠状病毒是一大类能够引起呼吸系统疾病，从而威胁人类健康的病毒．目前,对冠状病毒诱导细胞凋亡及其机制研究甚少.本研究以动物冠状病毒 猪流行性腹泻病毒(PEDV) 为模型探讨冠状病毒诱导细胞凋亡效应及其可能作用机制. 通过流式细胞术检测发现感染PEDV病毒后细胞凋亡率明显升高，且PEDV诱导细胞凋亡呈时间和剂量依赖性(P<0.05或P<0.01)；进一步研究发现,冠状病毒木瓜样蛋白酶（PLP）在病毒引起凋亡过程中起重要作用.实验发现,转染PEDV-PLP质粒后,caspase-3活化体表达水平明显升高. 提示冠状病毒PLP蛋白酶通过激活caspase-3在病毒诱导细胞凋亡过程中起着关键作用. 以上结果为研究人类冠状病毒PLP蛋白功能及其通过细胞凋亡调节宿主抗病毒天然免疫机制提供重要基础.

PEDV Coronavirus Induces Apoptosis through Activation of Caspase-3 by Papain-like Protease

Coronavirus is a life threatening virus, which may cause severe respiratory infectious disease in human as SARS and MERS. But at present, the apoptotic mechanisms induced by coronaviruses remain unclear. This study was to explore the potential mechanism of apoptosis induced by coronavirus, especially taking porcine epidemic diarrhea virus (PEDV), an animal coronavirus as a model. The results showed that the apoptosis rate of PEDV-infected cell was significantly higher than that of mock-infected group, and the apoptosis induced by PEDV showed time-and dose-dependent manner (P<0.05 or P<0.01). Next, the role of papain-like protease (PLP) of coronavirus in apoptosis was further investigated. The results showed that coronavirus PLP induced activation of caspase-3 in the HEK 293T when the cells were transfected with PEDV PLP plasmids. Moreover, PLP2 from other coronaviruses induced apoptosis through activation of caspases-3, implying that the ability to induce apoptosis is a shared attribute of coronavirus PLP2 and its homologs. Our results indicated that PLP-induced apoptosis might play a central role in coronavirus-induced apoptosis to inhibit the host antiviral innate immunity and facilitate coronaviral replication and pathogenesis.