Bagchi Parikshit, Inoue Takamasa, Tsai Billy
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States.
Elife. 2016 Dec 24;5:e21470. doi: 10.7554/eLife.21470.
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.
无包膜病毒的去稳定化会产生具有膜运输能力的病毒颗粒。在此，我们探究多瘤病毒SV40从内质网（ER）到细胞质的膜运输过程，这是一个决定性的感染步骤，在此步骤中，去稳定化启动了这种无包膜病毒的膜穿透过程。我们发现，内质网膜蛋白复合物（EMC）的一个成员EMC1促进了SV40的内质网膜运输和感染。令人惊讶的是，EMC1通过利用其预测的跨膜残基D961来结合并稳定嵌入膜中的部分去稳定化的SV40，从而防止病毒过早解体。EMC1依赖性稳定作用使SV40能够与一种细胞质提取复合物结合，该复合物将病毒喷射到细胞质中。因此，EMC1作为分子伴侣，将去稳定化的SV40维持在具有运输能力的状态。我们的研究结果揭示了一个新的原理，即协同的去稳定化-稳定化驱动无包膜病毒的膜运输。
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