Liquid-liquid phase separation underpins the formation of replication factories in rotaviruses.
Liquid-liquid phase separation underpins the formation of replication factories in rotaviruses.
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DOI：
10.15252/embj.2021107711
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发表时间：
2021-11-02
期刊：
影响因子：
--
通讯作者：
Borodavka A
中科院分区：
文献类型：
--
作者：
Geiger F;Acker J;Papa G;Wang X;Arter WE;Saar KL;Erkamp NA;Qi R;Bravo JP;Strauss S;Krainer G;Burrone OR;Jungmann R;Knowles TP;Engelke H;Borodavka A
RNA病毒诱导亚细胞细胞器的形成，这些细胞器提供有利于其复制的微环境。在这里，我们表明轮状病毒的复制工厂代表蛋白质-RNA凝聚体，它是通过病毒质形成蛋白NSP5和轮状病毒RNA伴侣蛋白NSP2的液-液相分离形成的。当混合时，这些蛋白质很容易在感染病毒的细胞质中形成生理上相关的低微摩尔浓度的凝聚体。早期感染阶段的冷凝物可以被1，6-己二醇以及从这些冷凝物中释放出轮状病毒转录物的丙二醇可逆地溶解。在感染的早期阶段，丙二醇治疗减少了病毒复制和凝析油形成蛋白NSP5的磷酸化。在晚期感染期间，这些冷凝物的物质性质发生了变化，并对丙二醇产生了抵抗力，这与NSP5的过度磷酸化相吻合。轮状病毒细胞质复制工厂组装的某些方面反映了其他核糖核蛋白颗粒的形成。这种富含病毒RNA的凝聚体支持多片段基因组的复制，是开发新的治疗方法的一个有吸引力的目标。病毒质是由NSP2和NSP5蛋白相分离形成的富含蛋白质/RNA的凝聚体，其被化合物破坏可减少轮状病毒的复制。
RNA viruses induce the formation of subcellular organelles that provide microenvironments conducive to their replication. Here we show that replication factories of rotaviruses represent protein‐RNA condensates that are formed via liquid–liquid phase separation of the viroplasm‐forming proteins NSP5 and rotavirus RNA chaperone NSP2. Upon mixing, these proteins readily form condensates at physiologically relevant low micromolar concentrations achieved in the cytoplasm of virus‐infected cells. Early infection stage condensates could be reversibly dissolved by 1,6‐hexanediol, as well as propylene glycol that released rotavirus transcripts from these condensates. During the early stages of infection, propylene glycol treatments reduced viral replication and phosphorylation of the condensate‐forming protein NSP5. During late infection, these condensates exhibited altered material properties and became resistant to propylene glycol, coinciding with hyperphosphorylation of NSP5. Some aspects of the assembly of cytoplasmic rotavirus replication factories mirror the formation of other ribonucleoprotein granules. Such viral RNA‐rich condensates that support replication of multi‐segmented genomes represent an attractive target for developing novel therapeutic approaches. Viroplasms represent protein/RNA‐rich condensates formed by phase‐separation of NSP2 and NSP5 proteins, whose disruption by chemical compounds reduces rotavirus replication.
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影响因子：
17.1
作者：
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通讯作者：
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通讯作者：
Brangwynne, Clifford P.
影响因子：
7.7
作者：
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通讯作者：
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