EMC1-dependent stabilization drives membrane penetration of a partially destabilized non-enveloped virus
EMC1-dependent stabilization drives membrane penetration of a partially destabilized non-enveloped virus
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DOI：
10.7554/elife.21470
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发表时间：
2016-12-24
期刊：
影响因子：
7.7
通讯作者：
Tsai, Billy
中科院分区：
文献类型：
--
作者：
Bagchi, Parikshit;Inoue, Takamasa;Tsai, Billy
非包膜病毒的失稳产生具有膜转运能力的病毒颗粒。在这里，我们探讨了多瘤病毒SV40内质网（ER）到细胞质膜的运输，这是一个决定性的感染步骤，其中不稳定启动了这种非包膜病毒的膜渗透。我们发现内质网膜蛋白复合物（EMC）的成员EMC1促进SV40 ER膜的运输和感染。令人惊讶的是，EMC1通过使用其预测的跨膜残基D961结合并稳定膜内部分不稳定的SV40，从而防止病毒过早解体。emc1依赖性稳定使SV40能够参与细胞质提取复合物，将病毒喷射到细胞质中。因此，EMC1作为分子伴侣，支持不稳定的SV40处于运输能力状态。我们的发现揭示了协调的不稳定-稳定驱动非包膜病毒的膜运输的新原理。
Destabilization of a non-enveloped virus generates a membrane transport-competent viral particle. Here we probe polyomavirus SV40 endoplasmic reticulum (ER)-to-cytosol membrane transport, a decisive infection step where destabilization initiates this non-enveloped virus for membrane penetration. We find that a member of the ER membrane protein complex (EMC) called EMC1 promotes SV40 ER membrane transport and infection. Surprisingly, EMC1 does so by using its predicted transmembrane residue D961 to bind to and stabilize the membrane-embedded partially destabilized SV40, thereby preventing premature viral disassembly. EMC1-dependent stabilization enables SV40 to engage a cytosolic extraction complex that ejects the virus into the cytosol. Thus EMC1 acts as a molecular chaperone, bracing the destabilized SV40 in a transport-competent state. Our findings reveal the novel principle that coordinated destabilization-stabilization drives membrane transport of a non-enveloped virus.