DNA循环释放因子WAPL抑制爱斯坦-巴尔病毒隐性膜蛋白表达,以维持高度限制的延迟I程序
Laura A Murray-Nerger1,2,3,4, Davide Maestri5,6, Xiang Liu7
1Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
PLoS pathogens
|September 6, 2024
概括
爱斯坦-巴尔病毒 (EBV) 利用宿主蛋白质WAPL抑制关键瘤基因,维持其在伯基特淋巴瘤中的延迟I程序. 破坏WAPL会改变EBV DNA循环,并重新激活病毒基因表达.
科学领域:
- 病毒学 病毒学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 癌症生物学 癌症生物学
背景情况:
- 爱斯坦-巴尔病毒 (EBV) 潜伏程序对于B细胞殖民至关重要,并与人类癌症有关.
- 维持EBV延迟I的表观遗传机制,以EBNA1表达为特征,仍然不完全理解.
- 高阶染色体结构影响病毒和宿主基因表达.
研究的目的:
- 调查Wings Apart-Like Protein Homolog (WAPL) 在维持EBV延迟I方面所起的作用.
- 探索WAPL如何影响EBV基因组架构和基因表达.
主要方法:
- 在伯基特淋巴瘤细胞中使用了WAPL淘汰 (KO).
- 使用Hi-C分析来评估EBV基因组DNA循环.
- 分析了病毒基因促进体的组织蛋白抑制标记.
主要成果:
- 华普尔KO抑制了LMP1和LMP2A的表达,将病毒程序转向延迟II.
- WAPL破坏改变了EBV基因组架构,在LMP促进体和oriLyt之间形成DNA循环.
- 降低了与WAPLKO细胞LMP1/2A去抑制相关的组织蛋白抑制标记.
结论:
- EBV可能将WAPL合起来,以负面调节潜膜蛋白表达,从而维持伯基特淋巴瘤的潜伏I程序.
- WAPL是控制EBV表观遗传状态和病毒瘤基因表达的关键宿主因子.
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