2013年3月13日讯 /生物谷BIOON/ -- 中国医学科学院病院生物学研究所，赵振东教授课题组于2月20日在Plos One上在线发表了名为The Interplays between Autophagy and Apoptosis Induced by Enterovirus 71的研究论文。
论文旨在研究，EV71感染诱导细胞自噬以及凋亡的相互调控关系。
EV71是人肠道病毒的一种，常引起儿童手足口病、病毒性咽峡炎，重症患儿可出现心肌炎、肺水肿、脑炎等，这些疾病多发生于儿童，尤其是3岁以下婴幼儿多发，少数病情较重，严重的会引起死亡。了解病毒与宿主的相互作用，在今后的药物筛选以及疫苗研究有重要的意义。
为此，赵振东教授及其团队以EV71安徽株感染人的横纹肌肉细胞（RD cells）作为模型，研究宿主与病毒的博弈。
研究显示，EV71感染RD细胞能显著的诱导细胞自噬以及细胞的凋亡。
细胞自噬与凋亡作为细胞的两种重要程序性死亡方式，两者在病毒感染过程之中是否有相互联系，或者相互作用？
研究人员利用基因沉默技术以及一系列的化学抑制剂研究发现，通过沉默Atg5，Beclin-1或者加入Wortmanin（PIK3抑制剂）抑制EV71感染过程中自噬体的形成，能显著抑制EV71感染所引起的细胞凋亡。然而用Chloroquine抑制自噬体与溶酶体的融合过程中，研究人员却发现细胞凋亡有明显的增加。
随后研究人员利用Z-VAD-FMK（caspase-3 抑制剂）抑制EV71感染所引起的细胞凋亡，观察细胞的自噬情况。研究发现，抑制细胞凋亡能增加LC3-I转化为LC3-II以及p62的降解。表明抑制EV71感染所引起的细胞凋亡能促进细胞的自噬。
此外研究人员还发现，抑制自噬体的形成或者细胞的凋亡能显著的降低病毒的毒力。这为抗EV71靶点的选择，以及药物的设计提供了一个新的思路。（生物谷Bioon.com）
doi:10.1371/journal.pone.0056966
The Interplays between Autophagy and Apoptosis Induced by Enterovirus 71
Xi X, Zhang X, Wang B, Wang T, Wang J, et al.
Background
Enterovirus 71 (EV71) is the causative agent of human diseases with distinct severity, from mild hand, foot and mouth disease to severe neurological syndromes, such as encephalitis and meningitis. The lack of understanding of viral pathogenesis as well as lack of efficient vaccine and drugs against this virus impedes the control of EV71 infection. EV71 virus induces autophagy and apoptosis; however, the relationship between EV71-induced autophagy and apoptosis as well as the influence of autophagy and apoptosis on virus virulence remains unclear.
Methodology/Principal Findings
In this study, it was observed that the Anhui strain of EV71 induced autophagy and apoptosis in human rhabdomyosarcoma (RD-A) cells. Additionally, by either applying chemical inhibitors or knocking down single essential autophagic or apoptotic genes, inhibition of EV71 induced autophagy inhibited the apoptosis both at the autophagosome formation stage and autophagy execution stage. However, inhibition of autophagy at the stage of autophagosome and lysosome fusion promoted apoptosis. In reverse, the inhibition of EV71-induced apoptosis contributed to the conversion of microtubule-associated protein 1 light chain 3-I (LC3-I) to LC3-II and degradation of sequestosome 1 (SQSTM1/P62). Furthermore, the inhibition of autophagy in the autophagsome formation stage or apoptosis decreased the release of EV71 viral particles.
Conclusions/Significance
In conclusion, the results of this study not only revealed novel aspect of the interplay between autophagy and apoptosis in EV71 infection, but also provided a new insight to control EV71 infection.
