Rabbit Hemorrhagic Disease Virus Non-structural Protein 6 Induces Apoptosis in Rabbit Kidney Cells
Rabbit Hemorrhagic Disease Virus Non-structural Protein 6 Induces Apoptosis in Rabbit Kidney Cells
复制标题
兔出血性疾病病毒非结构蛋白6诱导兔肾细胞凋亡
DOI：
10.3389/fmicb.2018.03308
复制
发表时间：
2019-01-09
影响因子：
5.2
通讯作者：
Wang, Fang
中科院分区：
文献类型：
--
作者：
Chen, Mengmeng;Liu, Xing;Wang, Fang
兔出血症（Rabbit Hemorrhagic Disease，RHD）是由兔出血症病毒（Rabbit Hemorrhagic Disease Virus，RHDV）引起的一种高度接触性传染病。先前的研究表明，RHDV诱导许多细胞类型的凋亡，虽然由RHDV诱导的细胞凋亡的分子机制还没有很好地理解。一个可能的因素是非结构蛋白6（NSP 6），一种3C样蛋白酶，在将病毒多聚蛋白前体加工成成熟的非结构蛋白中起重要作用。为了充分确定NSP 6的作用，本研究检查了该蛋白在兔（RK 13）和人（HeLa和HepG 2）细胞中异位表达的影响。我们发现，NSP 6抑制细胞活力和促进细胞凋亡，在所有三种细胞类型的剂量依赖性的方式。我们还鉴定了在RK 13细胞中增加的caspase-3、-8和-9活性，以及增加的Bax/Bcl 2 mRNA比率。从机制上讲，NSP 6诱导细胞凋亡的能力受到催化性His 27残基突变的损害。我们的研究表明，RHDV NSP 6可以诱导宿主细胞凋亡，可能是RHDV诱导的细胞凋亡和发病机制的重要贡献者。
Rabbit hemorrhagic disease (RHD) is a highly contagious disease caused by rabbit hemorrhagic disease virus (RHDV). Previous research has shown that RHDV induces apoptosis in numerous cell types, although the molecular mechanisms underlying the apoptosis induced by RHDV are not well understood. One possible factor is non-structural protein 6 (NSP6), a 3C-like protease that plays an important role in processing viral polyprotein precursors into mature non-structural proteins. To fully establish a role for NSP6, the present study examined the effects of ectopic expression of the protein in rabbit (RK13) and human (HeLa and HepG2) cells. We found that NSP6 suppressed cell viability and promoted apoptosis in all three cell types in a dose-dependent manner. We also identified increased caspase-3, -8, and -9 activities in RK13 cell, and an increased Bax to Bcl2 mRNA ratio. Mechanistically, the ability of NSP6 to induce apoptosis was impaired by mutation of the catalytic His27 residue. Our study has shown that RHDV NSP6 can induce apoptosis in host cells and is likely an important contributor to RHDV-induced apoptosis and pathogenesis.