The R2TP complex regulates paramyxovirus RNA synthesis
The R2TP complex regulates paramyxovirus RNA synthesis
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DOI：
10.1371/journal.ppat.1007749
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发表时间：
2019-05-01
期刊：
影响因子：
6.7
通讯作者：
Takeda, Makoto
中科院分区：
文献类型：
--
作者：
Katoh, Hiroshi;Sekizuka, Tsuyoshi;Takeda, Makoto
宿主蛋白对副粘病毒RNA合成的调节作用知之甚少。在这里，我们确定了一种新的副粘病毒RNA合成的Hsp90共伴侣R2TP复合物的调节机制。我们发现，R2TP复合物与副粘病毒聚合酶L蛋白相互作用，R2TP复合物的沉默导致腮腺炎病毒（MuV）基因转录的不受控制的上调，但不是基因组复制。R2TP复合物的调节对于MuV复制和逃避宿主先天免疫应答至关重要。R2TP复合物也调节麻疹病毒（MeV）RNA的合成，但其功能是抑制性的，对MeV没有好处，因为MeV在没有R2TP复合物的情况下逃避宿主的先天免疫反应。R2TP复合物作为关键宿主因子的鉴定为副粘病毒RNA合成的调节提供了新的思路。
The regulation of paramyxovirus RNA synthesis by host proteins is poorly understood. Here, we identified a novel regulation mechanism of paramyxovirus RNA synthesis by the Hsp90 co-chaperone R2TP complex. We showed that the R2TP complex interacted with the paramyxovirus polymerase L protein and that silencing of the R2TP complex led to uncontrolled upregulation of mumps virus (MuV) gene transcription but not genome replication. Regulation by the R2TP complex was critical for MuV replication and evasion of host innate immune responses. The R2TP complex also regulated measles virus (MeV) RNA synthesis, but its function was inhibitory and not beneficial to MeV, as MeV evaded host innate immune responses in the absence of the R2TP complex. The identification of the R2TP complex as a critical host factor sheds new light on the regulation of paramyxovirus RNA synthesis.