细胞外凝聚物 (ECs) 是HIV转录和潜伏再激活的内源调节剂
bioRxiv : the preprint server for biology
|September 30, 2024
概括
被SIV感染的的细胞外凝结物 (ECs) 激活潜伏的HIV. 然而,用THC治疗的的EC抑制了HIV的重新激活,这表明EC调节了HIV的持续性.
科学领域:
- 神经科学和病毒学
- 细胞外囊泡和艾滋病毒潜伏期
- 在病毒持久性中的大麻素治疗药物.
背景情况:
- 人类免疫缺陷病毒 (HIV) 的潜藏储存是实现治愈的主要障碍,因为它不受抗逆转录病毒疗法 (ART) 的影响.
- 了解控制艾滋病毒持续性的机制对于开发有效的治疗策略至关重要.
- 细胞外凝聚物 (ECs) 正在成为细胞过程的潜在调节者,包括病毒延迟.
研究的目的:
- 研究基底 (BG) 隔离的细胞外凝聚物 (ECs) 在重新编程HIV潜伏细胞中的作用.
- 探索Delta-9-tetrahydrocannabinol (THC) 在调节ECs以控制HIV重新激活方面的潜力.
主要方法:
- 利用后集成HIV潜伏的模型系统.
- 从未感染和感染SIV的大脑中分离和应用EC,有或没有THC治疗,到潜伏感染的细胞.
- 分析了病毒转录,抗原表达,病毒传播和宿主转录组/秘密组的改变.
主要成果:
- 来自感染SIV的ECs (VEHgadSIV ECs) 激活了潜伏的HIV转录和病毒抗原表达.
- 接受THC治疗的SIV感染的ECs (THC陰SIV ECs) 抑制了HIV转录,抗原表达和病毒再激活.
- THC加西SIVECs调节宿主基因表达和细胞因子分泌,促进抗炎特征并抑制促炎反应.
结论:
- 基底腺节EC可以作为内源因素,促进或抑制HIV潜伏活性.
- 长期服用低剂量的THC会使ECs充满抗炎物质,从而显著降低其激活潜伏HIV的能力.
- 电脑疗法是治疗策略的新目标,旨在控制艾滋病毒的持续性,并可能实现功能性治疗.
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