2013年3月13日訊 /生物谷BIOON/ -- 中國(guó)醫(yī)學(xué)科學(xué)院病院生物學(xué)研究所,，趙振東教授課題組于2月20日在Plos One上在線發(fā)表了名為T(mén)he Interplays between Autophagy and Apoptosis Induced by Enterovirus 71的研究論文。

論文旨在研究,，EV71感染誘導(dǎo)細(xì)胞自噬以及凋亡的相互調(diào)控關(guān)系,。

EV71是人腸道病毒的一種，常引起兒童手足口病,、病毒性咽峽炎,，重癥患兒可出現(xiàn)心肌炎、肺水腫,、腦炎等,，這些疾病多發(fā)生于兒童，尤其是3歲以下嬰幼兒多發(fā),，少數(shù)病情較重,，嚴(yán)重的會(huì)引起死亡。了解病毒與宿主的相互作用,，在今后的藥物篩選以及疫苗研究有重要的意義,。

為此，趙振東教授及其團(tuán)隊(duì)以EV71安徽株感染人的橫紋肌肉細(xì)胞（RD cells）作為模型,，研究宿主與病毒的博弈。

研究顯示,，EV71感染RD細(xì)胞能顯著的誘導(dǎo)細(xì)胞自噬以及細(xì)胞的凋亡。

細(xì)胞自噬與凋亡作為細(xì)胞的兩種重要程序性死亡方式,，兩者在病毒感染過(guò)程之中是否有相互聯(lián)系，或者相互作用,？

研究人員利用基因沉默技術(shù)以及一系列的化學(xué)抑制劑研究發(fā)現(xiàn),，通過(guò)沉默Atg5，Beclin-1或者加入Wortmanin（PIK3抑制劑）抑制EV71感染過(guò)程中自噬體的形成,，能顯著抑制EV71感染所引起的細(xì)胞凋亡,。然而用Chloroquine抑制自噬體與溶酶體的融合過(guò)程中，研究人員卻發(fā)現(xiàn)細(xì)胞凋亡有明顯的增加,。

隨后研究人員利用Z-VAD-FMK（caspase-3 抑制劑）抑制EV71感染所引起的細(xì)胞凋亡,，觀察細(xì)胞的自噬情況。研究發(fā)現(xiàn)，抑制細(xì)胞凋亡能增加LC3-I轉(zhuǎn)化為L(zhǎng)C3-II以及p62的降解,。表明抑制EV71感染所引起的細(xì)胞凋亡能促進(jìn)細(xì)胞的自噬,。

此外研究人員還發(fā)現(xiàn)，抑制自噬體的形成或者細(xì)胞的凋亡能顯著的降低病毒的毒力,。這為抗EV71靶點(diǎn)的選擇,，以及藥物的設(shè)計(jì)提供了一個(gè)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.