在SARS-CoV-2感染动物和人类宿主期间,核心线粒体基因的下调
Joseph W Guarnieri1,2,3, Joseph M Dybas2,3, Hossein Fazelinia2,3
1Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Science translational medicine
|August 9, 2023
概括
严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 感染会破坏宿主线粒体功能,抑制氧化酸化并促进糖解. 即使在病毒清除后,这种损伤仍然存在于心脏和脏等器官中,从而导致严重的COVID-19病理.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 已知严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 感染会影响各种宿主细胞过程.
- 线粒体功能障碍已与COVID-19的病理学有关.
研究的目的:
- 研究SARS-CoV-2对不同组织中线粒体基因表达的影响.
- 了解COVID-19期间和之后的病毒载荷,宿主反应和线粒体功能之间的关系.
主要方法:
- 从COVID-19患者的鼻和尸检组织中分析线粒体基因表达.
- 在SARS-CoV-2感染期间,对动物模型 (仓鼠和小鼠) 中线粒体基因表达的检查.
- 对宿主免疫防御途径和微RNA表达的评估.
主要成果:
- SARS-CoV-2抑制了核DNA编码的线粒体氧化酸化 (OXPHOS) 基因,并在鼻组织中诱导糖解.
- 在尸检组织中,肺线粒体基因转录恢复了,但心脏,脏和肝脏显示持续抑制核DNA编码的线粒体基因,诱导线粒体DNA转录和免疫激活.
- 动物模型显示早期的系统性线粒体基因表达变化,随着时间的推移,肺部恢复.
结论:
- 感染SARS-CoV-2引发了系统性宿主反应,抑制了线粒体基因转录,并诱导糖解,激活抗病毒防御.
- 心脏,脏和肝脏等器官的线粒体功能障碍即使在病毒清除和肺部恢复后也可能持续存在,可能导致严重的COVID-19病理.
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