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.
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。
