Herpes simplex virus type 1 abrogates the antiviral activity of Ch25h via its virion host shutoff protein
Herpes simplex virus type 1 abrogates the antiviral activity of Ch25h via its virion host shutoff protein
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1 型单纯疱疹病毒通过其病毒体宿主关闭蛋白消除 Ch25h 的抗病毒活性
DOI：
10.1016/j.antiviral.2017.04.004
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发表时间：
2017
影响因子：
7.6
通讯作者：
Zheng Chunfu
中科院分区：
文献类型：
--
作者：
You Hongjuan;Yuan Hui;Fu Wenkun;Su Chenhe;Wang Wei;Cheng Tong;Zheng Chunfu
胆固醇25-羟化酶（Ch25h）是一种干扰素诱导蛋白，最近的研究表明，它可以抑制许多包膜病毒的复制。然而，在本研究中，我们发现感染野生型（WT） HSV-1的细胞降低了Ch25h的表达，并且Ch25h的异位表达不能抑制WT-HSV-1的复制。通过筛选，发现HSV-1 UL41蛋白下调Ch25h的表达。此外，UL41通过降解Ch25h的mRNA来消除其抗病毒活性。此外，Ch25h的异位表达抑制了UL41-null突变体HSV-1 （R2621）的复制，而对WT-HSV-1无抑制作用，Ch25h的敲低不影响WT-HSV-1的复制，但促进了R2621的复制。首次证实HSV-1 UL41通过其内切酶活性逃避Ch25h的抗病毒功能。
Cholesterol 25-hydroxylase (Ch25h) is an interferon-inducible protein, and recent studies have demonstrated that it inhibited the replication of many enveloped viruses. However, in this study, we found that cells infected with wild-type (WT) HSV-1 reduced the expression of Ch25h, and ectopic expression of Ch25h could not inhibit the replication of WT-HSV-1. By screening assay, HSV-1 UL41 protein was found to down-regulate the expression of Ch25h. In addition, UL41 abrogated the antiviral activity of Ch25h via degrading its mRNA. Furthermore, ectopic expression of Ch25h inhibited the replication of UL41-null mutant HSV-1 (R2621), but not WT-HSV-1, and knockdown of Ch25h did not affect the replication of WT-HSV-1, but promoted the replication of the R2621. For the first time, HSV-1 UL41 was demonstrated to evade the antiviral function of Ch25h via its endonuclease activity.