寨卡病毒NS4B蛋白向TANK结合激酶1并抑制I型干扰素的产生
Maria B Sarratea1, Andrés Sánchez Alberti2, Daniela M Redolfi3
1Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Inmunología-IDEHU (UBA-CONICET), Junín 956, C1113AAD Buenos Aires, Argentina; W.M. Keck Laboratory for Structural Biology, University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, MD 20850, USA.
Biochimica et biophysica acta. General subjects
|October 6, 2023
概括
寨卡病毒NS4B蛋白质通过破坏TBK1/IRF3途径来抑制先天免疫反应,从而损害I型干扰素的产生. 这项研究提供了NS4B与TBK1结合的第一个生物物理证据,这对病毒免疫逃避至关重要.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 病毒感染通过核酸感应触发I型干扰素 (IFN-I) 生产,这是一个关键的抗病毒天生的免疫机制.
- 弗拉维病毒,包括寨卡病毒 (ZIKV),通常编码非结构性蛋白质来逃避宿主免疫反应,但这些机制尚不清楚.
研究的目的:
- 研究ZIKV NS4B蛋白在抑制IFN-I诱导通路中的作用.
- 描述ZIKV NS4B与与先天免疫有关的宿主蛋白之间的生物物理相互作用.
主要方法:
- 基于细胞的测试被用来评估ZIKV NS4B对干扰素调节因子 (IRF),NF-κB,细胞因子分泌和干扰素刺激基因 (ISG) 的影响.
- 使用表面等离子体共振 (SPR) 来分析复合ZIKV NS4B和TANK结合激酶1 (TBK1) 之间的体外相互作用.
主要成果:
- 发现ZIKV NS4B可以抑制IRF激活,减少IFN-β和IL-6分泌,并限制早期ISG诱导.
- SPR分析表明ZIKV NS4B和TBK1 (KD = 3.7 × 10-6 M) 之间的直接结合相互作用,NS4B的N终端区域调解了这种相互作用.
结论:
- ZIKV NS4B破坏了TBK1/IRF3轴,损害了IFN-β的产生,从而影响了核酸传感级联.
- 这项研究提供了关于ZIKV NS4B-TBK1相互作用的第一个生物物理数据,突出了NS4B在逃避早期天生的免疫反应中的作用.
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