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Grace C Roberts¹, Nicola J Stonehouse¹, Mark Harris¹

¹School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK.

|February 26, 2025

概括

奇孔古尼亚病毒nsP3蛋白通过其宏观域抑制NF-κB信号传递,这对病毒复制至关重要. 这种nsP3功能影响病毒生命周期和传染性.

科学领域:

病毒学病毒学
分子生物学分子生物学
免疫学免疫学免疫学

背景情况:

奇孔古尼亚病毒 (CHIKV) 非结构蛋白3 (nsP3) 在病毒生命周期中没有明确的作用.
nsP3具有具有RNA和ADP-核糖酶结合能力和ADP-核糖酶酸酶活性的宏域.
ADP-ribosylation影响信号通路,包括NF-κB的激活.

研究的目的:

研究CHIKV nsP3宏域在NF-κB信号传递中的作用.
为了确定nsP3是否可以在CHIKV感染或表达期间调节NF-κB激活.
评估nsP3宏域活动对CHIKV复制和传染性的影响.

主要方法:

评估CHIKV感染细胞和表达nsP3.3的细胞中的NF-κB激活.
利用TNFα诱导和测试NF-κB激活的抑制.
使用nsP3宏域的D10A突变物来评估其酶活性的重要性.
测量CHIKV感染性与野生类型和突变nsP3表达.

主要成果:

虽然TNFα治疗适度降低了CHIKV标位,但CHIKV感染并没有诱导或阻止NF-κB激活.
nsP3的宫外表达抑制了基底和TNFα诱导的NF-κB激活.
通过nsP3抑制NF-κB需要宏域的ADP-ribose结合和酶活性,正如D10A突变所示.
D10A宏域突变显著降低了CHIKV感染力.

结论:

nsP3宏域通过抑制NF-κB信号传递,在CHIKV复制中发挥关键作用.
nsP3调节NF-κB激活的能力对于有效的CHIKV生命周期进展至关重要.
针对nsP3-NF-κB相互作用可能是CHIKV抗病毒疗法的策略.

关键词:

它们是ADP-ribose.在 NF-κBB 中.奇孔古尼亚病毒病毒.宏观领域宏观领域在 nsP3P3 中.

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