Division of Infectious Diseases, Department of Medicine, University of Utah School of Medicine, 30 North 1900 East, Room 4B319, Salt Lake City, UT, 84132, USA.
Curr HIV/AIDS Rep. 2020 Jun;17(3):219-225. doi: 10.1007/s11904-020-00496-0.
To review the potential use of senotherapeutics, pharmacologic agents that target senescent cells, in addressing HIV-1 persistence.
Treated HIV-1 infection results in a state of immune exhaustion, which may involve reprogramming of infected and bystander cells toward a state of cellular senescence. Aging research has recently uncovered pathways that make senescent cells uniquely susceptible to pharmacologic intervention. Specific compounds, known as senotherapeutics, have been identified that interrupt pathways senescent cells depend on for survival. Several of these pathways are important in modulating the cellular microenvironment in chronically and latently infected cells. Strategies targeting these pathways may prove useful in combating both HIV-1 persistence and HIV-1-associated immune exhaustion. Senotherapeutics have recently been described as potential therapeutics for aging-associated diseases driven by senescent cells. Recently, correlations have emerged between HIV-1 infection, senescence, lifelong chronic infection, and viral persistence. New insights and therapies targeting cellular senescence may offer a novel strategy to address both HIV-1 persistence and immune exhaustion induced by chronic viral infection.
探讨针对衰老细胞的治疗药物（衰老细胞疗法）在解决 HIV-1 持续感染中的潜在应用。
经治疗的 HIV-1 感染会导致免疫耗竭状态，这可能涉及到感染细胞和旁观者细胞向细胞衰老状态的重编程。衰老研究最近揭示了使衰老细胞特别容易受到药物干预的途径。已经确定了一些特定的化合物，称为衰老细胞疗法，它们可以阻断衰老细胞生存所依赖的途径。这些途径中的几个在调节慢性和潜伏感染细胞的细胞微环境中非常重要。针对这些途径的策略可能有助于对抗 HIV-1 持续感染和 HIV-1 相关的免疫耗竭。衰老细胞疗法最近被描述为针对由衰老细胞驱动的与衰老相关疾病的潜在治疗方法。最近，HIV-1 感染、衰老、终身慢性感染和病毒持续存在之间出现了相关性。针对细胞衰老的新见解和疗法可能为解决慢性病毒感染引起的 HIV-1 持续感染和免疫耗竭提供新策略。
