BRD9作为HIV-1潜伏性调节因子起作用
Tsz-Yat Luk1,2, Lok-Yan Yim1,2, Runhong Zhou1,2
1AIDS Institute, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region of China.
概括
基蛋白含有蛋白9 (BRD9) 的抑制会重新激活潜伏的HIV-1储存器,这是HIV-1治愈的关键步骤. 这一发现为开发有效的延迟逆转剂来打击艾滋病毒提供了一个新的目标.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 潜伏的病毒储备阻碍了HIV-1治疗.
- "震惊和杀死"战略旨在重新激活和消除这些水库.
- 目前的潜伏逆转剂 (LRAs) 在完全激活潜伏HIV-1的有效性有限.
研究的目的:
- 为了确定HIV-1潜伏的新型调节者.
- 为了研究含有odomain的蛋白9 (BRD9) 在HIV-1潜伏期中的作用.
主要方法:
- 抑制,基因枯竭和BRD9.9的蛋白质降解.
- 在T细胞系,人类休息记忆CD4+T细胞和来自ART的HIV-1 (PWH) 感染者的PBMC中进行测试.
- CUT&RUN DNA 测序,转录组学和药理学分析.
主要成果:
- 在不同细胞类型中,BRD9抑制始终重新激活HIV-1潜伏期.
- 抑制BRD9与抑制BRD4协同作用,以增强HIV-1的产生.
- 发现BRD9可以结合HIV-1 LTR促进体,与HIV-1 Tat.竞争.
- 下游宿主目标ATAD2和MTHFD2被确定为HIV-1潜伏的BRD9调节器.
结论:
- BRD9是一种HIV-1潜伏期的新型调节剂.
- 准BRD9代表了HIV-1治疗研究的一个有希望的战略.
- 了解BRD9的机制提供了对HIV-1潜伏期宿主-病原体相互作用的见解.
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