转录因子EB (TFEB) 与RagC的相互作用在肠道病毒D68感染期间被破坏
Alagie Jassey1, Noah Pollack1, Michael A Wagner1
1Department of Microbiology and Immunology and Center for Pathogen Research, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Journal of virology
|June 18, 2024
概括
转录因子EB (TFEB) 对肠道病毒D68的复制和传播至关重要. EV-D68蛋白酶分裂TFEB,破坏其功能并促进病毒释放,这表明TFEB是抗病毒标.
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:
- 肠道病毒D68 (EV-D68) 引起严重的呼吸系统疾病和急性软骨髓炎.
- 目前没有针对EV-D68.8的疫苗或抗病毒药物.
- EV-D68利用细胞自途径进行复制.
研究的目的:
- 研究转录因子EB (TFEB) 在EV-D68感染中的作用.
- 阐明EV-D68与TFEB相互作用的机制.
- 确定TFEB作为潜在的抗病毒标.
主要方法:
- TFEB的敲击实验评估其对病毒复制的影响.
- 通过EV-D68 3C蛋白酶进行TFEB裂变的分析.
- 过度表达TFEB突变体以研究其在病毒退出和自中的作用.
- 在自性缺陷细胞上的实验.
主要成果:
- TFEB的淘汰减少了EV-D68的基因组RNA复制,但没有病毒的进入.
- EV-D68 3C蛋白酶切割TFEB,破坏其与RagC和 lysosomal运输的相互作用.
- 对于EV-D68的非溶性释放,TFEB裂变和随后的细胞溶性定位至关重要.
- 一个缺乏RagC结合域的TFEB突变抑制了自并增强了病毒的退出.
结论:
- 对于EV-D68生命周期的多个阶段来说,TFEB是一个关键的宿主因素.
- EV-D68通过蛋白酶分裂来操纵TFEB功能,以促进病毒复制和退出.
- 准TFEB为开发针对EV-D68.8的新型抗病毒疗法提供了一个有前途的战略.
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