The regulation of persistent Borna disease virus infection by RNA silencing factors in human cells
The regulation of persistent Borna disease virus infection by RNA silencing factors in human cells
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人体细胞中RNA沉默因子对博尔纳病病毒持续感染的调节
DOI：
10.1016/j.bbrc.2023.03.069
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发表时间：
2023
影响因子：
3.1
通讯作者：
Takahashi Tomoko
中科院分区：
文献类型：
--
作者：
Kaneko Yuka;Naito Yuui;Koide Rie;Parrish Nicholas F.;Takahashi Tomoko
病毒感染诱导多种细胞免疫应答。一些病毒诱导抗病毒细胞因子的产生，内源性基因表达的改变和细胞凋亡;然而，其他病毒复制而不诱导这些反应，使它们能够持续感染细胞。博尔纳病病毒1型（BoDV-1）感染可导致致命的免疫介导的脑炎，包括在人类中，但体外细胞感染通常是持续的。这种持续感染的调控机制尚不清楚。在这里，我们表明RNA沉默增强子TRBP正调控人细胞中的BoDV RNA水平。TRBP的敲低降低了持续感染细胞中的BoDV RNA水平，而TRBP的过表达增加了BoDV RNA水平。为了研究这种现象的机制，我们进行了免疫沉淀试验，发现TRBP与BoDV RNA相互作用。此外，我们进行了细胞分级分离，这表明BoDV的持续感染不会改变TRBP和其他RNA沉默因子在细胞中的定位。我们的研究结果表明，在人类细胞中RNA沉默因子对持续BoDV感染的调节。
Viral infection induces diverse cellular immune responses. Some viruses induce the production of antiviral cytokines, alterations of endogenous gene expression, and apoptosis; however, other viruses replicate without inducing such responses, enabling them to persistently infect cells. Infection by Borna disease virus type 1 (BoDV-1) can result in fatal immune-mediated encephalitis, including in humans, yet infection of cellsin vitrois generally persistent. The regulatory mechanisms underlying this persistent infection remain unclear. Here, we show that an enhancer of RNA-silencing, TRBP, positively regulates BoDV RNA level in human cells. Knockdown of TRBP decreased BoDV RNA levels in persistently-infected cells, whereas overexpression of TRBP increased BoDV RNA levels. To investigate the mechanism underlying this phenomenon, we performed immunoprecipitation assays and found that TRBP interacts with BoDV RNA. Furthermore, we performed cell fractionation, which revealed that persistent infection with BoDV does not alter the localization of TRBP and other RNA silencing factors in cells. Our results showed the regulation of persistent BoDV infection by RNA-silencing factors in human cells.