Enhanced human enterovirus 71 infection by endocytosis inhibitors reveals multiple entry pathways by enterovirus causing hand-foot-and-mouth diseases.
Enhanced human enterovirus 71 infection by endocytosis inhibitors reveals multiple entry pathways by enterovirus causing hand-foot-and-mouth diseases.
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内吞作用抑制剂增强人肠道病毒71型感染揭示肠道病毒引起手足口病的多种进入途径
DOI：
10.1186/s12985-017-0913-3
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发表时间：
2018-01-03
期刊：
影响因子：
4.8
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Yuan M;Yan J;Xun J;Chen C;Zhang Y;Wang M;Chu W;Song Z;Hu Y;Zhang S;Zhang X
背景人类肠道病毒71（EV 71）以前已知通过网格蛋白或小窝介导的内吞途径进入细胞。然而，我们观察到抑制网格蛋白和发动蛋白介导的内吞作用的氯丙嗪（CPZ）或dynasore（DNS）在特定细胞类型中不抑制EV 71细胞进入。因此，目前的知识由EV71进入mechanisms是不完整的。MethodsViral感染进行了检查，通过流式细胞术或终点稀释试验。通过免疫荧光或假病毒感染监测病毒进入。各种抑制剂用于操纵内吞途径。细胞蛋白被敲低siRNA。ResultsCPZ和DNS没有抑制，而是增强病毒感染A549细胞，而他们抑制感染在其他细胞测试。我们进一步发现，CPZ不影响EV71与靶细胞的结合，也不影响病毒的翻译和复制，但增强了病毒进入A549细胞。免疫荧光显微镜进一步证实了这种增加的进入。通过siRNA实验，我们发现CPZ增强EV71感染并不需要网格蛋白介导的内吞作用。最后，CPZ也增强感染柯萨奇病毒A16在A549 cellus.ConclusionsCPZ和DNS，以前报道的EV71进入抑制剂，而可能会导致增加病毒感染在特定的细胞类型。CPZ和DNS增加了病毒的进入，而不是病毒生命周期的其他步骤。因此，我们的研究表明，一个未知的动力蛋白独立的进入途径，利用肠道病毒引起手足口病。
BackgroundHuman enterovirus 71 (EV71) was previously known to enter cells through clathrin or caveolar mediated endocytic pathways. However, we observed chlorpromazine (CPZ) or dynasore (DNS), which inhibit clathrin and dynamin mediated endocytosis, did not suppress EV71 cell entry in particular cell types. So the current knowledge of entry mechanisms by EV71 is not complete.MethodsViral infection was examined by flow cytometry or end-point dilution assays. Viral entry was monitored by immunofluorescence or pseudoviral infections. Various inhibitors were utilized for manipulating endocytic pathways. Cellular proteins were knockdown by siRNA.ResultsCPZ and DNS did not inhibit but rather enhance viral infection in A549 cells, while they inhibited infections in other cells tested. We further found CPZ did not affect EV71 binding to target cells and failed to affect viral translation and replication, but enhanced viral entry in A549 cells. Immunofluorescence microscopy further confirmed this increased entry. Using siRNA experiment, we found that the enhancement of EV71 infection by CPZ did not require the components of clathrin mediated endocytosis. Finally, CPZ also enhanced infection by Coxackivirus A16 in A549 cells.ConclusionsCPZ and DNS, previously reported as EV71 entry inhibitors, may rather lead to increased viral infection in particular cell types. CPZ and DNS increased viral entry and not other steps of viral life cycles. Therefore, our study indicated an unknown dynamin-independent entry pathway utilized by enteroviruses that cause Hand-Foot-and-Mouth Diseases.
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作者：
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