依赖pH的包裹病毒的内体融合需要离子通道TRPM7
Catherine A Doyle1, Gregory W Busey1, Wesley H Iobst1
1Department of Pharmacology, University of Virginia, Charlottesville, VA, USA.
Nature communications
|October 1, 2024
概括
TRPM7通道对于包裹病毒进入细胞至关重要. 阻止TRPM7可以防止多种危险病毒感染,提供潜在的广泛的抗病毒策略.
科学领域:
- 病毒学 病毒学
- 细胞生物学 细胞生物学
- 离子通道生理学 离子通道生理学
背景情况:
- 流行病威胁通常涉及包裹病毒,这些病毒利用内体酸性化进入细胞.
- 受体介导的内细胞结核和随后的内体酸性化是许多病毒感染的关键步骤.
研究的目的:
- 为了研究短暂受体潜在拉斯7 (TRPM7) 通道在包裹病毒的内体体融合中的作用.
- 确定TRPM7是否是广泛抗病毒疗法的潜在目标.
主要方法:
- 利用多个病毒感染系统,表达来自各种病毒的信封糖蛋白.
- 在TRPM7功能存在或不存在的情况下,评估了对病毒感染的细胞保护.
- 研究了TRPM7离子通道活性对内体酸性化的必要性.
主要成果:
- 丢失TRPM7可以保护人免受拉萨,LCMV,埃博拉,流感,MERS,SARS-CoV-1和SARS-CoV-2的感染.
- TRPM7离子通道活动对于酸性化病毒载体内基因组至关重要.
- TRPM7在酸化中的作用是针对病毒内分体的,而不是一般的内分体通路.
结论:
- TRPM7离子通道活动对于低pH依赖的包裹病毒的内体体融合是不可或缺的.
- 提出了一个模型,其中TRPM7通过阴离子逆流促进了质子向内分体输送.
- 准TRPM7为开发针对包裹病毒的广泛抗病毒药物提供了一个有前途的战略.
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