The TRiC chaperonin controls reovirus replication through outer-capsid folding.
The TRiC chaperonin controls reovirus replication through outer-capsid folding.
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DOI：
10.1038/s41564-018-0122-x
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发表时间：
2018-04
影响因子：
28.3
通讯作者：
Dermody TS
中科院分区：
文献类型：
--
作者：
Knowlton JJ;Fernández de Castro I;Ashbrook AW;Gestaut DR;Zamora PF;Bauer JA;Forrest JC;Frydman J;Risco C;Dermody TS
病毒是维持整个生命周期的分子机器，需要在宿主细胞内复制。在整个感染周期中，病毒和细胞成分相互作用，以推进产生后代病毒体所需的多步骤过程。尽管在理解病毒-宿主蛋白质相互作用组方面取得了进展，但关于在感染期间起作用的细胞因子，特别是在复制的末端步骤中起作用的细胞因子，仍有许多有待发现。在RNA干扰筛选中，我们将真核伴侣蛋白TRiC（也称为CCT）鉴定为哺乳动物呼肠孤病毒复制中晚期事件所需的细胞因子。我们发现TRiC在呼肠孤病毒复制中通过一种机制起作用，该机制涉及病毒σ3外衣壳蛋白折叠成能够组装到病毒颗粒上的形式。TRiC还与密切相关的病毒的同源衣壳蛋白复合。我们的数据定义了TRiC在病毒组装过程中的关键功能，并提出了这种机制在相关无包膜病毒中保守的可能性。这些结果还提供了对TRiC蛋白底物的深入了解，并为开发TRiC的小分子抑制剂作为潜在的抗病毒治疗药物建立了理论基础。
Viruses are molecular machines sustained through a life cycle that requires replication within host cells. Throughout the infectious cycle, viral and cellular components interact to advance the multistep process required to produce progeny virions. Despite progress made in understanding the virus-host protein interactome, much remains to be discovered about the cellular factors that function during infection, especially those operating at terminal steps in replication. In an RNA interference screen, we identified the eukaryotic chaperonin TRiC (also called CCT) as a cellular factor required for late events in the replication of mammalian reovirus. We discovered that TRiC functions in reovirus replication through a mechanism that involves the folding of the viral σ3 outer-capsid protein into a form capable of assembling onto virus particles. TRiC also complexes with homologous capsid proteins of closely related viruses. Our data define a critical function for TRiC in the viral assembly process and raise the possibility that this mechanism is conserved in related nonenveloped viruses. These results also provide insight into TRiC protein substrates and establish a rationale for the development of small-molecule inhibitors of TRiC as potential antiviral therapeutics.
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影响因子：
5.4
作者：
Becker, MM;Goral, MI;Dermody, TS
通讯作者：
Dermody, TS
影响因子：
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影响因子：
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影响因子：
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