在COVID-19中SARS-CoV-2线粒体的代谢和表观基因组重编程
Joseph W Guarnieri1, Jeffrey A Haltom1, Yentli E Soto Albrecht2
1Center for Mitochondrial and Epigenomic Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Pharmacological research
|April 13, 2024
概括
SARS-CoV-2 感染通过抑制线粒体氧化酸化 (OXPHOS),增加活性氧物种 (ROS) 来破坏细胞代谢. 这种代谢转变推动病毒复制,并可能导致长期COVID症状.
科学领域:
- 细胞的新陈代谢
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
背景情况:
- 感染SARS-CoV-2会改变宿主细胞的功能.
- 了解代谢重编程对于抗病毒策略至关重要.
研究的目的:
- 为了研究SARS-CoV-2对细胞代谢途径的影响.
- 为了确定病毒传播必不可少的代谢点.
主要方法:
- 由SARS-CoV-2调节的代谢途径的全面调查.
- 评估途径抑制剂对病毒传播的影响.
主要成果:
- SARS-CoV-2 强烈抑制了线粒体的氧化酸化 (OXPHOS).
- 增加的线粒体ROS (mROS) 稳定HIF-1α,将新陈代谢重定向到糖解和酸途径 (PPP) 进行病毒生物发生.
- mROS诱导mtDNA释放,激活天生的免疫力.
- 病毒蛋白Orf8和Orf10重组nDNA和mtDNAOXPHOS基因表达,可能通过表观基因组修改.
结论:
- SARS-CoV-2 劫持宿主代谢以促进病毒复制.
- 代谢重编程和病毒蛋白对表观基因组的潜在改变可能是长期COVID病原体的基础.
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