Activation of the RLR/MAVS Signaling Pathway by the L Protein of Mopeia Virus.
Activation of the RLR/MAVS Signaling Pathway by the L Protein of Mopeia Virus.
复制标题
Mopeia 病毒 L 蛋白激活 RLR/MAVS 信号通路。
DOI：
10.1128/jvi.01292-16
复制
发表时间：
2016
影响因子：
5.4
通讯作者：
Xiao Gengfu
中科院分区：
文献类型：
--
作者：
Zhang Lei-Ke;Xin Qi-Lin;Zhu Sheng-Lin;Wan Wei-Wei;Wang Wei;Xiao Gengfu
沙粒病毒科包括几种重要的人类病原体，可引起严重的出血热，极大地威胁着公共卫生。作为先天免疫系统的主要组成部分，RLR/MAVS信号通路参与识别病毒组分并启动抗病毒活性。已有报道沙粒病毒感染可抑制先天性免疫应答，致病性沙粒病毒的NP和Z蛋白可破坏RLR/MAVS信号传导，从而抑制I型干扰素（IFN-I）的产生。然而，最近的研究表明，在某些沙粒病毒感染的细胞中IFN-I水平升高。沙粒病毒感染诱导IFN-I应答的机制尚不清楚。在这项研究中，我们确定了Mopeia病毒（MOPV）的L聚合酶（Lp），一种旧世界（OW）沙粒病毒，可以激活RLR/MAVS途径，从而诱导IFN-I的产生。这种激活与Lp的RNA依赖性RNA聚合酶活性有关。本研究为进一步研究沙粒病毒与先天免疫系统之间的相互作用以及阐明沙粒病毒的致病机制奠定了基础。沙粒病毒的NP和某些Z蛋白抑制RLR/MAVS信号通路已被广泛接受。负责激活RLR/MAVS信号通路的病毒组分仍有待确定。在本研究中，我们首次证明MOPV（OW沙粒病毒）的Lp可以激活RLR/MAVS信号通路，从而诱导IFN-I的产生。基于我们的研究结果，我们提出了动态相互作用之间存在的LP产生的RNA，NP和RLR/MAVS信号通路，这些相互作用的结果可能会决定最终的IFN-I反应模式：升高或降低。我们的研究为IFN-I在沙粒病毒感染期间如何被激活提供了一个可能的解释，并可能帮助我们深入了解不同沙粒病毒组分与先天免疫系统之间形成的相互作用。
The family Arenaviridae includes several important human pathogens that can cause severe hemorrhagic fever and greatly threaten public health. As a major component of the innate immune system, the RLR/MAVS signaling pathway is involved in recognizing viral components and initiating antiviral activity. It has been reported that arenavirus infection can suppress the innate immune response, and NP and Z proteins of pathogenic arenaviruses can disrupt RLR/MAVS signaling, thus inhibiting production of type I interferon (IFN-I). However, recent studies have shown elevated IFN-I levels in certain arenavirus-infected cells. The mechanism by which arenavirus infection induces IFN-I responses remains unclear. In this study, we determined that the L polymerase (Lp) of Mopeia virus (MOPV), an Old World (OW) arenavirus, can activate the RLR/MAVS pathway and thus induce the production of IFN-I. This activation is associated with the RNA-dependent RNA polymerase activity of Lp. This study provides a foundation for further studies of interactions between arenaviruses and the innate immune system and for the elucidation of arenavirus pathogenesis.IMPORTANCEDistinct innate immune responses are observed when hosts are infected with different arenaviruses. It has been widely accepted that NP and certain Z proteins of arenaviruses inhibit the RLR/MAVS signaling pathway. The viral components responsible for the activation of the RLR/MAVS signaling pathway remain to be determined. In the current study, we demonstrate for the first time that the Lp of MOPV, an OW arenavirus, can activate the RLR/MAVS signaling pathway and thus induce the production of IFN-I. Based on our results, we proposed that dynamic interactions exist among Lp-produced RNA, NP, and the RLR/MAVS signaling pathway, and the outcome of these interactions may determine the final IFN-I response pattern: elevated or reduced. Our study provides a possible explanation for how IFN-I can become activated during arenavirus infection and may help us gain insights into the interactions that form between different arenavirus components and the innate immune system.