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The TRiC chaperonin controls reovirus replication through outer-capsid folding.
Nature Microbiology ( IF 28.3 ) Pub Date : 2018-Apr-01 , DOI: 10.1038/s41564-018-0122-x
Jonathan J. Knowlton , Isabel Fernández de Castro , Alison W. Ashbrook , Daniel R. Gestaut , Paula F. Zamora , Joshua A. Bauer , J. Craig Forrest , Judith Frydman , Cristina Risco , Terence S. Dermody

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 T-complex protein-1 (TCP-1) ring complex (TRiC; also called CCT for chaperonin containing TCP-1) 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 folding the viral σ3 major 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 non-enveloped 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.

中文翻译:

TRiC伴侣蛋白通过衣壳的折叠控制呼肠孤病毒的复制。

病毒是维持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子代病毒体所需的多步过程。尽管在了解病毒-宿主蛋白相互作用组方面取得了进展,但是关于感染期间起作用的细胞因子,尤其是那些在复制的最终步骤起作用的细胞因子,仍有很多待发现。在RNA干扰筛选中,我们确定了真核生物伴侣蛋白T复合蛋白1(TCP-1)环复合物(TRiC;也称为包含TCP-1的伴侣蛋白的CCT)是哺乳动物复制后期事件所需的细胞因子。呼肠孤病毒。我们发现TRiC通过一种机制将呼肠孤病毒复制起作用,该机制涉及将病毒σ3主要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在病毒装配过程中的关键功能,并提高了这种机制在相关的非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小分子抑制剂作为潜在的抗病毒治疗剂奠定了基础。我们的数据定义了TRiC在病毒装配过程中的关键功能,并提高了这种机制在相关的非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小分子抑制剂作为潜在的抗病毒治疗剂奠定了基础。我们的数据定义了TRiC在病毒装配过程中的关键功能,并提高了这种机制在相关的非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小分子抑制剂作为潜在的抗病毒治疗剂奠定了基础。
更新日期:2018-03-13
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