KSHV基因组含有构成性和乳液诱导增强剂
Nilabja Roy Chowdhury1, Vyacheslav Gurevich1, Meir Shamay1
1Daniella Lee Casper Laboratory in Viral Oncology, Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.
Journal of virology
|May 2, 2024
概括
研究人员在卡波西的肉瘤相关疹病毒 (KSHV) 中确定了关键的调控元素,包括构成性和流性增强剂和沉声器. 这些元素,特别是作为"病毒超级增强剂"的终端重复,对于控制KSHV基因表达和病毒生命周期过渡至关重要.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 卡波西肉瘤相关性疹病毒 (KSHV) 是一种人类致癌性疹病毒.
- 在KSHV基因表达上,对潜伏性,溶性复制和瘤发生有着严格的调节.
- 像增强剂和沉默剂这样的远端 cis-regulatory 元素控制基因表达.
研究的目的:
- 系统地识别KSHV基因组中的cis调节元件 (增强剂和减噪剂).
- 研究这些元素在KSHV感染的潜伏和溶解阶段的功能.
- 阐明这些元素在调节KSHV基因表达和病毒生命周期中的作用.
主要方法:
- 从KSHV基因组中克隆开放的染色质区域,该基因组是 luciferase 记者基因的下游基因.
- 在受感染和未受感染的细胞中对增强剂和静音剂活性进行功能性测试.
- 激活CRISPR和干扰技术以确定增强剂-基因连接.
主要成果:
- 在延迟关联核抗原促进剂的上游确定了一种沉声器.
- 在K12p-OriLyt-R和ORF29 Intron区域 (特定于组织) 中发现了两个构成增强剂.
- 鉴定出了四种性诱导增强剂 (OriLyt-L,PANp,ALTp,TRs),对RTA有反应.
- 终端重复 (TRs) 作为一个"病毒超级增强器",集成LANA和RTA效应.
结论:
- 已识别的沉声器和增强剂提供了对KSHV基因调节的更深入的理解.
- 该TRs作为一个关键的病毒超级增强剂,控制KSHV的延迟-lytic过渡.
- 这些监管要素是了解KSHV相关恶性瘤的关键目标.
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