KDM6A-KMT2D-p300轴通过调解病毒受体表达来调节对各种冠状病毒的敏感性
Jin Wei1,2, Mia Madel Alfajaro1,2, Wesley L Cai3
1Department of Laboratory Medicine, Yale School of Medicine, New Haven, Connecticut, United States of America.
PLoS pathogens
|July 6, 2023
概括
组织素脱甲基酶KDM6A通过调节病毒受体表达来促进各种冠状病毒感染. 抑制KDM6A-KMT2D-p300复合体提供了针对SARS-CoV-2等冠状病毒的潜在治疗策略.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 了解宿主因素对于识别冠状病毒病原机制和治疗点至关重要.
- 基因组脱甲基酶KDM6A在冠状病毒感染中的作用尚未完全理解.
研究的目的:
- 研究KDM6A在各种冠状病毒感染机制中的作用.
- 确定参与KDM6A介导的冠状病毒易感性的分子途径和蛋白质复合体.
- 探索将KDM6A综合体作为泛冠状病毒治疗策略的潜在目标.
主要方法:
- 评估KDM6A对SARS-CoV,SARS-CoV-2,MERS-CoV和MHV感染的影响.
- 使用机理学研究研究KDM6A与KMT2D和p300的相互作用.
- 分析KDM6A-KMT2D-p300复合体对病毒受体增强剂 (例如,ACE2) 的局部化.
- 评估p300抑制对病毒受体表达和抗感染能力的有效性.
主要成果:
- KDM6A促进了各种冠状病毒的感染,而不依赖于其脱甲基酶活性.
- KDM6A调节了多个冠状病毒受体的表达,包括ACE2,DPP4和Ceacam1.
- KDM6A-KMT2D-p300复合体对于调节ACE2表达至关重要.
- 小分子抑制p300取消了ACE2和DPP4的表达,使其对SARS-CoV-2变种和MERS-CoV.产生抗性.
结论:
- KDM6A-KMT2D-p300复合体在赋予对各种冠状病毒的易感性方面发挥着关键作用.
- 针对这种复杂的,特别是p300活动,是一个有希望的泛冠状病毒治疗方法.
- 这一发现为开发针对当前和新兴冠状病毒的广泛抗病毒疗法开辟了道路.
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