爱斯坦-巴尔病毒通过颠覆B细胞激活和生殖中心调节位置来逃避限制性宿主染色质关闭
Elliott D SoRelle1, Nicolás M Reinoso-Vizcaino2, Joanne Dai2
1Department of Molecular Genetics and Microbiology, Duke Center for Virology, Duke University School of Medicine, Durham, NC 27710, USA; Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC 27710, USA.
爱斯坦-巴尔病毒 (EBV) 感染改变了B细胞染色质的可访问性,模仿了生殖中心的表型. EBV核抗原调节B细胞激活,存活和免疫逃避,影响淋巴发育.
科学领域:
- 免疫学 免疫学 免疫学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 病毒学 病毒学
背景情况:
- 染色体可访问性对于基因表达和细胞反应至关重要.
- 病原体可以操纵宿主细胞的基因调节.
- 爱斯坦-巴尔病毒 (EBV) 感染B细胞并影响其行为.
研究的目的:
- 在EBV感染期间研究单个B细胞中的动态色素景观.
- 了解EBV如何操纵B细胞基因表达和表型.
- 在B单元中确定EBV驱动的监管机制.
主要方法:
- 转化酶可访问的染色体测序 (scATAC-seq) 的单细胞测定.
- 单细胞RNA测序 (scRNA-seq) 是一种方法.
- 染色体免疫沉降测序 (ChIP-seq).
- 多学科数据的生物信息集成.
- 基因淘汰验证. 基因淘汰验证.
主要成果:
- 由于抗病毒传感和DNA损伤,EBV感染减少了因被阻止的B细胞的全球染色质可访问性.
- 繁殖EBV+B细胞表现出类似于体内生殖中心 (GC) B细胞的染色质特征.
- EBV诱导暗区 (DZ),光区 (LZ) 和后GC B细胞染色质状态,即使BCL6下调.
- 全基因组的预测表明,EBV核抗原 (EBNA) 在控制GC B细胞表型.
- MEF2C和NFE2L2已被验证为EBV诱导的GC表型和EBNA相关位点的调节剂.
结论:
- EBV动态重塑B细胞染色质的可访问性,以模仿GC表型.
- EBNAs在调节EBV感染的B细胞激活,生存和免疫逃避方面发挥着关键作用.
- 已识别的调节器和机制为EBV驱动的淋巴发生和宿主相互作用提供了洞察力.
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