超越病毒抑制:解码线粒体-免疫轴在艾滋病毒相关的炎症和免疫功能障碍
Tracy Okine1, Eleanor Hill1, Kate Sheran1
1Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Frontiers in cellular and infection microbiology
|November 3, 2025
概括
抗逆转录病毒疗法 (ART) 可以治疗艾滋病毒,但与线粒体功能障碍相关的持续性炎症导致并发症. 向线粒免疫轴为艾滋病毒治疗提供了新的治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 线粒体生物学 线粒体生物学
- 病毒学 病毒学
背景情况:
- 用ART治疗艾滋病毒改善了结果,但慢性免疫激活和炎症在艾滋病毒感染者 (PLWH) 中仍然存在.
- 这种残留炎症有助于长期的并发症,如神经认知障碍和心血管疾病.
- 线粒体在调节细胞代谢和免疫反应方面发挥着至关重要的作用,在PLWH中,它们的功能受到干扰.
研究的目的:
- 审查线粒免疫轴在艾滋病毒发病过程中的作用.
- 探索HIV和ART如何影响线粒体功能和炎症信号.
- 讨论针对线粒体功能障碍和炎症的潜在治疗干预措施.
主要方法:
- 文献综述侧重于线粒体与HIV免疫系统之间的相互作用.
- 分析包括氧化酸化 (OxPhos) 失调,炎酶激活和纯能受体信号传递在内的机制.
- 检查潜在的治疗策略,如纯能抗剂.
主要成果:
- 艾滋病毒和ART破坏了线粒体功能,导致反应性氧物种 (ROS) 和氧化线粒体DNA (mtDNA) 的释放.
- 这些线粒体衍生信号激活NLRP3炎症体,促进IL-1β和其他促炎细胞因子的分泌.
- 过量的线粒体ATP激活纯能受体 (P2X1,P2X7),进一步传播炎症信号.
结论:
- 线粒体是HIV免疫功能的中央调节者.
- 准线性免疫轴,包括OxPhos,炎细胞和纯能信号传递,为解决PLWH慢性炎症提供了一个有希望的方法.
- 为了全面治疗艾滋病毒,需要转向恢复免疫代谢平衡的范式转变,超越病毒抑制.
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