细胞Notch1蛋白质以Rta-依赖的方式促进KSHV的重新激活
Jennifer DeCotiis-Mauro1,2, Sun M Han1,2, Helena Mello1,2
1Department of Microbiology, Biochemistry, and Molecular Genetics, Rutgers Biomedical and Health Sciences, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.
Journal of virology
|July 8, 2024
概括
构成性口活动对于卡波西肉瘤相关性疹病毒 (KSHV) 的重新激活和强大的传染性病毒产生至关重要. 虽然Notch单独无法重新激活KSHV,但它与病毒蛋白Rta合作,增强病毒基因表达.
科学领域:
- 病毒学 病毒学
- 细胞生物学 细胞生物学
- 信号传输 信号传输
背景情况:
- 诺奇信号通路与卡波西的肉瘤相关的疹病毒 (KSHV) 感染和发病有关.
- 诺奇通路的关键组成部分RBP-Jk在KSHV的活性化过程中与病毒蛋白Rta相互作用.
研究的目的:
- 调查构成性Notch活动在KSHV再激活和病毒病原发生中的作用.
- 阐明Notch信号影响KSHV生产的机制.
主要方法:
- 使用定量记者病毒系统来评估Notch异型体的KSHV重新激活能力.
- 使用玛分泌酶抑制剂 (GSI) 和主导负MAML1来抑制Notch信号.
- 使用siRNA专门抑制Notch1,并分析病毒转录和传染性KSHV产生.
主要成果:
- 构成性口活动对于传染性KSHV的稳健生产至关重要.
- 抑制Notch信号显著降低了KSHV的产生和特定的病毒基因转录.
- 激活的Notch1在重新激活过程中与病毒DNA形成促进子特异性复合体,与Rta.合作.
结论:
- 构成性口活动是有效的KSHV重新激活和生产所必需的.
- 激活的Notch1作为一种亲病毒因子,在病毒DNA复合体中与Rta,MAML1和RBP-Jk合作.
- 缺口信号代表了KSHV在其生命周期中操纵的关键宿主因素.
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