Department of Clinical Laboratory, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241001, Anhui, China.
Department of Nuclear Medicine, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241001, Anhui, China.
Microb Pathog. 2022 Jun;167:105569. doi: 10.1016/j.micpath.2022.105569. Epub 2022 May 8.
As a single-stranded RNA virus, vesicular stomatitis virus (VSV) causes influenza-like clinical symptoms in infected individuals. Type-I interferon signaling pathway plays a vital role in inhibiting VSV replication. It has been shown that RNF114 (RING finger protein 114) acts as an E3 ubiquitin ligase to regulate the type-I interferon signaling pathway. In contrast, the effects of RNF114 from Chinese sturgeon or sea perch remain controversial. In the present study, we reported the effect of human RNF114 on VSV infection. Overexpression of RNF114 promoted VSV replication, while depletion of RNF114 reduced viral replication. We further found that RNF114 inhibited type-I interferon production via interacting with mitochondrial antiviral signaling protein (MAVS). Moreover, in vivo experiments demonstrated that RNF114 could also accelerate VSV replication and virus-induced inflammation in lung tissues. Collectively, our findings supported that RNF114 negatively regulated the type-I interferon signaling pathway during VSV replication, providing novel and favorable insights into clinical treatment of VSV infection.
作为一种单链 RNA 病毒，水疱性口炎病毒（VSV）会导致感染个体出现类似流感的临床症状。I 型干扰素信号通路在抑制 VSV 复制方面起着至关重要的作用。已有研究表明，RNF114（环指蛋白 114）作为一种 E3 泛素连接酶，可调节 I 型干扰素信号通路。相比之下，中华鲟或鲈鱼的 RNF114 的作用仍存在争议。在本研究中，我们报告了人源 RNF114 对 VSV 感染的影响。过表达 RNF114 会促进 VSV 复制，而 RNF114 的缺失则会降低病毒复制。我们进一步发现，RNF114 通过与线粒体抗病毒信号蛋白（MAVS）相互作用抑制 I 型干扰素的产生。此外，体内实验表明，RNF114 还可加速 VSV 在肺组织中的复制和病毒诱导的炎症反应。综上所述，我们的研究结果表明，RNF114 在 VSV 复制过程中负调控 I 型干扰素信号通路，为 VSV 感染的临床治疗提供了新的、有前景的思路。
