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淋巴细胞性冠状腺炎 (Lymphocytic choriomeningitis arenavirus) 病毒需要细胞COPI和AP-4复合体才能有效地产生病毒

Owen Byford^1,2, Amelia B Shaw^1,2, Hiu Nam Tse^1,2

¹School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.

Journal of virology

|February 9, 2024

概括

淋巴细胞冠状淋巴炎病毒 (LCMV) 需要宿主细胞COPI和AP-4复合体才能有效复制和释放. 抑制这些复合体可显著减少传染性LCMV的产生,突出显示它们在病毒输出中的作用.

科学领域:

病毒学病毒学
细胞生物学细胞生物学
分子生物学分子生物学

背景情况:

淋巴细胞冠状腺炎病毒 (LCMV) 是一个模型的竞技病毒,一个双分割的负感RNA病毒.
感染LCMV可以导致致命的疾病,特别是在免疫受损的个体.
了解LCMV与宿主细胞机械的相互作用,对于开发抗病毒策略至关重要.

研究的目的:

识别宿主细胞贩运组件对于LCMV繁殖至关重要.
阐明COPI和AP-4复合体在LCMV生命周期中的作用.
研究COPI和AP-4抑制对传染性病毒产生的影响.

主要方法:

利用一种表达GFP的重组LCMV和一个精选的siRNA库来选宿主因子.
采用FLAG标记的LCMV糖蛋白 (GP-1) 救援病毒来可视化病毒组件的局部化.
使用Brefeldin A (BFA),一种ARF-I抑制剂,以药理上抑制COPI和AP-4复合体的形成.

主要成果:

一个屏幕确定了COPI和AP-4复合物的子单元,这些子单元对于LCMV的繁殖是必要的.
感染LCMV导致COPI和AP-4组件与病毒核蛋白 (NP) 和GP-1共同局部化.
BFA治疗显著抑制了传染性LCMV的释放,标位在12小时内下降了50倍,在24小时内下降了600倍以上,而不影响RNA合成或NP表达.

结论:

COPI和AP-4复合体是有效的LCMV输出所需的关键宿主细胞因子.
这些复合体在LCMV繁殖周期的后期阶段发挥作用,特别是后基因表达.
针对涉及COPI和AP-4的细胞贩运途径可能代表针对LCMV和其他竞技病毒的新疗法.

关键词:

在AP-4中使用AP-4.这就是COPI.在 LCMV 中,LCMV 是竞技场病毒竞技场病毒

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