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慢性炎症介导 HIV 感染中的脑损伤:对治疗策略的相关性。

Chronic inflammation mediates brain injury in HIV infection: relevance for cure strategies.

机构信息

Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA.

出版信息

Curr Opin Neurol. 2020 Jun;33(3):397-404. doi: 10.1097/WCO.0000000000000807.

Abstract

PURPOSE OF REVIEW

Chronic inflammation is a major component of HIV infection, the effects of which can be devastating in the central nervous system (CNS). Protecting the brain is, therefore, critical as efforts proceed to cure HIV infection by reactivating latent viral reservoirs and driving immune responses. We review the clinical presentation and pathology findings of inflammatory processes in the CNS in patients managed with ART and the drivers of these processes.

RECENT FINDINGS

Chronic inflammation is associated with increased mortality and morbidity and HIV infection increases the risk for chronic diseases, especially cognitive impairment. Latent viral reservoirs, including microglia and tissue macrophages, contribute to inflammation in the CNS. Inflammation is generated and maintained through residual viral replication, dysregulation of infected cells, continuously produced viral proteins and positive feedback loops of chronic inflammation. Novel therapeutics and lifestyle changes may help to protect the CNS from immune-mediated damage.

SUMMARY

As therapies are developed to cure HIV, it is important to protect the CNS from additional immune-mediated damage. Adjunctive therapies to restore glial function, reduce neuroinflammation and systemic inflammation, and inhibit expression of viral proteins are needed.

摘要

目的综述

慢性炎症是 HIV 感染的一个主要组成部分,其对中枢神经系统(CNS)的影响可能是毁灭性的。因此,保护大脑至关重要,因为人们正在努力通过重新激活潜伏的病毒库和驱动免疫反应来治愈 HIV 感染。我们回顾了接受 ART 治疗的患者中枢神经系统中炎症过程的临床表现和病理学发现,以及这些过程的驱动因素。

最近的发现

慢性炎症与死亡率和发病率的增加有关,HIV 感染会增加患慢性疾病的风险,尤其是认知障碍。潜伏的病毒库,包括小胶质细胞和组织巨噬细胞,会导致中枢神经系统的炎症。炎症是通过残余病毒复制、受感染细胞的失调、持续产生的病毒蛋白和慢性炎症的正反馈循环产生和维持的。新型治疗方法和生活方式的改变可能有助于保护 CNS 免受免疫介导的损伤。

总结

随着治疗 HIV 的疗法的发展,保护 CNS 免受额外的免疫介导的损伤非常重要。需要辅助疗法来恢复神经胶质功能、减少神经炎症和全身炎症,并抑制病毒蛋白的表达。

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