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TRIM21通过M1的依赖于ubiquitination的降解来限制流感A病毒的复制

Lulu Lin^1,2, Xingbo Wang¹, Zhen Chen³

¹MOA Key Laboratory of Animal Virology, Zhejiang University Center for Veterinary Sciences, Hangzhou, China.

|June 21, 2023

概括

三方基因含有蛋白21 (TRIM21) 通过降解矩阵蛋白1 (M1) 来限制流感A病毒 (IAV). 这种宿主因子驱动病毒突变,限制了IAV的复制和哺乳动物的病原性.

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:

三方基因含有蛋白21 (TRIM21) 是主体抗病毒反应中的关键E3泛基因酶.
针对流感A病毒 (IAV) 的TRIM21的特定抗病毒机制和光谱尚未完全理解.

研究的目的:

阐明TRIM21对抗流感A病毒 (IAV) 的机制和抗病毒谱.
研究TRIM21在宿主病毒共同进化和病毒适应中的作用.

主要方法:

在不同亚型中研究了TRIM21与IAV矩阵蛋白1 (M1) 的相互作用.
利用位点定向突变发生来分析TRIM21-M1的结合和无处不在.
评估了TRIM21和M1突变对病毒复制和致病性的影响.
从历史的IAV分离物中对M1蛋白进行了序列分析.

主要成果:

通过向M1.1,TRIM21抑制了H3,H5和H9 IAV亚型的复制.
TRIM21将M1与残留物R95结合,并针对K242进行K48无化和蛋白质体降解.
在M1中R95K或K242R突变赋予TRIM21的耐药性,增强病毒复制和致病性.
分析显示,R95K突变在适应哺乳动物的IAV菌株中逐渐积累,这表明宿主驱动的进化.

结论:

TRIM21通过降低M1. 作用作为对特定IAV亚型的宿主限制因子.
TRIM21驱动IAV M1中的适应性突变,促进病毒适应哺乳动物宿主.
了解这种宿主病毒相互作用,可以了解流感病毒的进化和病原性.

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