致癌病毒劫持SOX18的先驱功能,以增强病毒的持久性
bioRxiv : the preprint server for biology
|July 9, 2025
概括
卡波西卡波西 (Kaposi Kaposi) 是一个
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- 卡波西肉瘤疹病毒 (KSHV) 导致终身感染,通常发生在淋巴内皮细胞 (LEC) 中.
- 对持续的KSHV感染而言,维护病毒间歇性基因组至关重要,但其调控尚未完全理解.
- 病毒蛋白LANA对于KSHV病例稳定性至关重要.
研究的目的:
- 为了研究KSHV用于插曲性基因组维护的细胞类型特定机制.
- 识别导致KSHV插曲在淋巴内皮细胞中持续存在的宿主因素.
主要方法:
- 研究了内皮特异性转录因子SOX18在KSHV感染中的作用.
- 利用了SOX18和SWI/SNF复杂子单元BRG1.1.的遗传和药理学破坏.
- 评估病毒插曲负载和KSHV感染的标志.
主要成果:
- 在LEC中,KSHV劫持了SOX18的开拓性功能,以维持病毒发作.
- 拉纳招募SWI/SNF复杂子单元BRG1到SOX18,增强病毒基因组持久性的染色质可访问性.
- 破坏SOX18或BRG1显著减少病毒插曲负载和感染的标志.
结论:
- KSHV利用内皮特异性转录因子SOX18进行高效的环节性基因组维护.
- 这种相互作用通过招募染色体重塑复合物来促进病毒的持久性.
- 针对这种途径提供了控制KSHV感染的潜在策略.
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