EV71诱导不完整的细胞自噬促进自身复制

EV71 induces incomplete cellular autophagy to promote self-replication

目的探讨肠道病毒71型(enterovirus 71,EV71)与细胞自噬之间的关系以及细胞自噬对病毒复制的影响。方法用雷帕霉素、氯喹(chloroquine,CQ)、3-甲基腺嘌呤(3-Methyladenine,3-MA)对人横纹肌肉瘤细胞(rhabdomyosarcoma,RD)进行前处理,用Western blot和噬斑试验检测自噬的不同阶段对病毒复制的影响。结果EV71感染能够诱导RD细胞发生不完整的自噬。CQ处理组EV71的复制被促进,而雷帕霉素和3-MA处理组病毒的复制水平降低。mTOR是影响EV71复制的关键分子,用雷帕霉素抑制mTOR可抑制病毒RNA的合成。结论自噬的不同阶段对病毒复制的影响亦不同,抑制自噬溶酶体降解,病毒复制被促进,而抑制自噬早期阶段或促进自噬,病毒复制水平降低。mTOR可在RNA水平上影响EV71的复制。

Objective To investigate the relationship between enterovirus 71(EV71)and autophagy and the effect of autophagy on viral replication.Methods RD cells were pretreated with rapamycin,Chloroquine(CQ)and 3-methyladenine(3-MA).The effects of different stages of autophagy on viral replication were detected by Western blotting and plaque assay.Results The study showed that EV71 infection could induce incomplete autophagy in RD cells.Replication of EV71 was promoted in the CQ treatment group,while the level of replication of the rapamycin and 3-MA treatment groups was reduced.Further studies have shown that mTOR is a key molecule affecting EV71 replication,and inhibition of mTOR by rapamycin can inhibit the synthesis of viral RNA.Conclusions The effects of different stages of autophagy on viral replication are also different.Inhibition of autophagic lysosome degradation promotes viral replication,while inhibition of the early stage of autophagy or promotion of autophagy reduces the level of viral replication.mTOR can affect the replication of EV71 at RNA level.