Ye Zhongde, Wong Chung Kai, Li Peng, Xie Yong
Department of Biology, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China.
Biochim Biophys Acta. 2008 Dec;1780(12):1383-7. doi: 10.1016/j.bbagen.2008.07.009. Epub 2008 Jul 28.
Severe acute respiratory syndrome (SARS) coronavirus (CoV) spread from China to more than 30 countries, causing severe outbreaks of atypical pneumonia and over 800 deaths worldwide. CoV primarily infects the upper respiratory and gastrointestinal tract; however, SARS-CoV has a unique pathogenesis because it infects both the upper and lower respiratory tracts and leads to human respiratory diseases. SARS-CoV genome has shown containing 14 open reading frames (ORFs) and 8 of them encode novel proteins. Previous reports show that overexpression of ORF-3a, ORF-3b and ORF-7a induce apoptosis. In this report, we demonstrate that overexpression of ORF-6 also induces apoptosis and that Caspase-3 inhibitor and JNK inhibitor block ORF-6 induced apoptosis. Importantly, the protein level of ER chaperon protein, GRP94, was up-regulated when ORF-6 was overexpressed. All these data suggest that ORF-6 induces apoptosis via Caspase-3 mediated, ER stress and JNK-dependent pathways.
严重急性呼吸综合征（SARS）冠状病毒（CoV）从中国传播到30多个国家，在全球范围内引发了严重的非典型肺炎疫情，并导致800多人死亡。冠状病毒主要感染上呼吸道和胃肠道；然而，SARS-CoV具有独特的发病机制，因为它既能感染上呼吸道，也能感染下呼吸道，并导致人类呼吸道疾病。SARS-CoV基因组显示包含14个开放阅读框（ORF），其中8个编码新蛋白。先前的报道表明，ORF-3a、ORF-3b和ORF-7a的过表达会诱导细胞凋亡。在本报告中，我们证明ORF-6的过表达也会诱导细胞凋亡，并且半胱天冬酶-3抑制剂和JNK抑制剂可阻断ORF-6诱导的细胞凋亡。重要的是，当ORF-6过表达时，内质网伴侣蛋白GRP94的蛋白水平上调。所有这些数据表明，ORF-6通过半胱天冬酶-3介导的、内质网应激和JNK依赖的途径诱导细胞凋亡。
