帕拉米克索病毒矩阵蛋白调节宿主细胞转化,通过细胞质中的外连接复杂相互作用来调节宿主细胞转化
Chuan-Tien Hung1, Griffin D Haas1, Ruth E Watkinson1
1Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
bioRxiv : the preprint server for biology
|September 16, 2024
概括
帕拉米克索病毒 (PMVs) 使用其矩阵蛋白来抑制宿主细胞蛋白质合成,并通过与核心外连结复合体 (cEJC) 相互作用来增强病毒复制. 这种相互作用将核糖体重定向到病毒mRNA,提供潜在的抗病毒点.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 病毒,包括帕拉米克索病毒 (PMVs),操纵宿主细胞翻译进行复制.
- 对于PMVs调节宿主翻译的具体机制,人们的理解尚不完全.
研究的目的:
- 系统地研究PMV如何干扰宿主细胞转化.
- 为了确定病毒因素和宿主相互作用参与这个过程.
- 探索针对这些相互作用进行抗病毒策略的潜力.
主要方法:
- 纯甲基化标签,以评估新生的合成.
- 个别病毒基因的过度表达和感染野生型病毒与基因删除病毒.
- 复制器系统 (rNiV-NPL),多体形分析和互动组分析 (NiV-矩阵).
- 宿主因子 (eIF4AIII,cEJC) 的siRNA敲除和病毒标位的确定.
主要成果:
- PMVs显著抑制宿主新生的合成,主要由病毒基质蛋白介导.
- PMV矩阵增强病毒蛋白翻译,并抑制宿主蛋白在翻译层面的表达.
- 在细胞质中,PMV矩阵与宿主核心外连结复合体 (cEJC) 相互作用.
- 消耗cEJC显著增强PMV复制,但不是其他病毒,如SARS-CoV-2或流感.
- siRNA对eIF4AIII的淘汰模仿了病毒矩阵对蛋白质合成的影响.
结论:
- PMV矩阵蛋白是抑制宿主转化和促进病毒复制的关键因素.
- 确定了一种涉及PMV矩阵和宿主cEJC之间的相互作用的新机制.
- 这种相互作用将细胞核糖体重定向,使病毒mRNA转化优于宿主mRNA.
- PMV矩阵-cEJC相互作用代表了开发针对PMVs的广泛抗病毒疗法的潜在目标.
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