登革热病毒 2 型 NS2B 靶向 MAVS 和 IKKε 以逃避抗病毒固有免疫反应。
Dengue Virus 2 NS2B Targets MAVS and IKKε to Evade the Antiviral Innate Immune Response.
机构信息
The First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang 550002, Guizhou Province, P.R. China.
Department of Parasitology; Provincial Key Laboratory of Modern Pathogen Biology, College of Basic Medical Sciences, Guizhou Medical University, Guiyang, 550025, P.R. China.
出版信息
J Microbiol Biotechnol. 2023 May 28;33(5):600-606. doi: 10.4014/jmb.2210.10006. Epub 2023 Feb 15.
Dengue virus (DENV) is a widespread arbovirus. To efficiently establish infection, DENV evolves multiple strategies to hijack the host innate immune response. Herein, we examined the inhibitory effects of DENV serotype 2 (DENV2) nonstructural proteins on RIG-I-directed antiviral immune response. We found that DENV2 NS2A, NS2B, NS4A, and NS4B significantly inhibited RIG-I-mediated IFN-β promoter activation. The roles of NS2B in RIG-I-directed antiviral immune response are unknown. Our study further showed that NS2B could dose-dependently suppress RIG-I/MAVS-induced activation of IFN-β promoter. Consistently, NS2B significantly decreased RIG-I- and MAVS-induced transcription of , , and . Mechanistically, NS2B was found to interact with MAVS and IKKε to impair RIG-I-directed antiviral response. Our findings demonstrated a previously uncharacterized function of NS2B in RIG-I-mediated antiviral response, making it a promising drug target for anti-DENV treatments.
登革热病毒（DENV）是一种广泛传播的虫媒病毒。为了有效地建立感染，DENV 进化出多种策略来劫持宿主先天免疫反应。在此，我们研究了 DENV 血清型 2（DENV2）非结构蛋白对 RIG-I 介导的抗病毒免疫反应的抑制作用。我们发现 DENV2 NS2A、NS2B、NS4A 和 NS4B 显著抑制了 RIG-I 介导的 IFN-β 启动子激活。NS2B 在 RIG-I 介导的抗病毒免疫反应中的作用尚不清楚。我们的研究进一步表明，NS2B 可以剂量依赖性地抑制 RIG-I/MAVS 诱导的 IFN-β 启动子激活。一致地，NS2B 显著降低了 RIG-I 和 MAVS 诱导的 、 和 的转录。在机制上，发现 NS2B 与 MAVS 和 IKKε 相互作用，从而损害 RIG-I 介导的抗病毒反应。我们的研究结果表明 NS2B 在 RIG-I 介导的抗病毒反应中具有以前未被描述的功能，使其成为抗 DENV 治疗的有前途的药物靶点。
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