卡波西的肉瘤疹病毒利用DNA损伤反应来循环化其基因组
Shijun Li1,2, Bing Liu1,2, Min Tan1,2
1Departments of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Nucleic acids research
|January 5, 2024
概括
涉及ATM和DNA-PKcs的DNA损伤反应 (DDR) 途径对于简单性疹病毒-1 (HSV-1) 和卡波西肉瘤相关性疹病毒 (KSHV) 基因组循环化至关重要,使终身潜伏感染成为可能.
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:
- 疹病毒通过未知的机制循环化其DNA基因组来建立终身隐性感染.
- 卡波西肉瘤相关性疹病毒 (KSHV) 是一种疹病毒,存在于染色体外,并与KSHV相关的疾病有关.
研究的目的:
- 阐明感染后KSHV基因组循环化的机制.
- 研究DNA损伤反应 (DDR) 激酶在疹病毒循环化和延迟中的作用.
主要方法:
- 在受感染细胞中评估KSHV基因组循环化.
- 使用DDR激酶抑制剂和野生类型/突变激酶 (ATM,DNA-PKcs) 的表达.
- 雇佣的NHEJ和HR记者分析和研究HSV-1循环.
主要成果:
- KSHV基因组循环化发生迅速且独立于病毒蛋白表达.
- ATM和DNA-PKcs对于KSHV循环和延迟是必不可少的;它们的缺席严重损害了这一过程.
- 非同源DNA末端连接 (NHEJ) 和同源重组 (HR) 途径有助于KSHV循环.
- ATM和DNA-PKcs也在HSV-1循环中发挥作用,而γH2AX在两种病毒中都没有作用.
结论:
- DNA损伤反应 (DDR) 途径,特别是ATM和DNA-PKcs,调解KSHV和HSV-1基因组循环.
- 这种DDR介导的循环化是建立疹病毒延迟的潜在通用机制.
- 针对这种机制可以提供新的策略来预防疹病毒疾病.
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