UBE1a Suppresses Herpes Simplex Virus-1 Replication.
UBE1a Suppresses Herpes Simplex Virus-1 Replication.
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DOI：
10.3390/v12121391
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发表时间：
2020-12-04
期刊：
影响因子：
--
通讯作者：
Fujimuro M
中科院分区：
文献类型：
--
作者：
Ikeda M;Ito A;Sekine Y;Fujimuro M
单纯疱疹病毒-1 （HSV-1）是引起唇疱疹、角膜炎、脑膜炎和脑炎的病原体。hsv -1编码的ICP5是病毒复制过程中衣壳组装所必需的主要衣壳蛋白。泛素化是一种翻译后修饰，在调节细胞事件(如蛋白酶体降解、蛋白质运输、抗病毒反应和病毒事件（如感染和病毒复制的建立）中起着关键作用。ub活化酶（E1，也称为UBE1）参与泛素化的第一步。然而，目前尚不清楚UBE1是否参与病毒感染或细胞抗病毒反应。在这里，我们发现UBE1a抑制HSV-1复制并促进抗病毒反应。UBE1a抑制剂PYR-41增加HSV-1的产生。免疫荧光分析显示，UBE1a高表达细胞ICP5低表达，反之亦然。PYR-41和shRNA抑制UBE1a可增加hsv -1感染细胞中ICP5的表达。UBE1a降低和延缓了ICP5蛋白的表达，但不影响ICP5 mRNA的转录或ICP5蛋白的降解。此外，UBE1a与ICP27相互作用，两者部分共定位于Hsc70疫源/病毒诱导的伴侣蛋白富集（VICE）结构域。PYR-41减少了UBE1a和ICP27的共定位。因此，我们的研究结果为UBE1a在细胞对病毒感染的反应中的机制提供了见解。
Herpes simplex virus-1 (HSV-1) is the causative agent of cold sores, keratitis, meningitis, and encephalitis. HSV-1-encoded ICP5, the major capsid protein, is essential for capsid assembly during viral replication. Ubiquitination is a post-translational modification that plays a critical role in the regulation of cellular events such as proteasomal degradation, protein trafficking, and the antiviral response and viral events such as the establishment of infection and viral replication. Ub-activating enzyme (E1, also named UBE1) is involved in the first step in the ubiquitination. However, it is still unknown whether UBE1 contributes to viral infection or the cellular antiviral response. Here, we found that UBE1a suppressed HSV-1 replication and contributed to the antiviral response. The UBE1a inhibitor PYR-41 increased HSV-1 production. Immunofluorescence analysis revealed that UBE1a highly expressing cells presented low ICP5 expression, and vice versa. UBE1a inhibition by PYR-41 and shRNA increased ICP5 expression in HSV-1-infected cells. UBE1a reduced and retarded ICP5 protein expression, without affecting transcription of ICP5 mRNA or degradation of ICP5 protein. Additionally, UBE1a interacted with ICP27, and both partially co-localized at the Hsc70 foci/virus-induced chaperone-enriched (VICE) domains. PYR-41 reduced the co-localization of UBE1a and ICP27. Thus, our findings provide insights into the mechanism of UBE1a in the cellular response to viral infection.
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