HIV脑内存储库——功能性治愈的另一障碍

The neglected brain reservoirs: a barrier to an HIV cure

减小HIV感染者体内病毒储存库的规模是实现HIV功能性治愈的基础。"Shock and kill"(赶尽杀绝)策略首先激活静息的病毒储存库,进而通过强化的联合抗逆转录病毒治疗或联合治疗性免疫以清除这些病毒储存库。HIV可在中枢神经系统内的血管旁巨噬细胞、小胶质细胞和星状细胞形成潜伏感染,这些脑内病毒储存库也须要被清除。然而,中枢神经系统是隔离于外周其他部位的独立的HIV药理学避难所。不但如此,脑内潜伏感染的细胞也与体内主要的病毒储存库记忆性T细胞不同。由于大脑的独特环境,使得清除或减少这些脑内病毒储存库十分困难。本文将就目前对于中枢神经系统病毒储存库的认识加以介绍,对清除脑内储存库所面临的困难进行讨论,并对清除病毒储存库的潜在方法进行总结,为实现HIV功能性治愈提供一定的思路与方法。

Reducing the size of virus reservoirs is fundamental for HIV positive patients to achieve an HIV functional cure. The 〝shock and kill〞strategy enables the reactivation of latent reservoirs, which will be followed by an intensive combined antiretroviral therapy（c ART） or therapeutic immunization to clear the reservoirs. HIV can latently infected cells such as perivascular macrophages, microglial cells, and astrocytes in the central nervous system（CNS）, and this brain reservoirs need to be eliminated. However, the CNS is a pharmacological sanctuary isolated from other parts of the body. In addition, latently infected cells in the brain are rather different from the main memory T-cells in the virus reservoirs. So it might be difficult to eliminate or reduce brain reservoirs since the CNS has these unique characteristics. In order to provide some ideas and methods for the realization of functional cure of HIV, this review will give an introduction on the existing understanding of viral reservoirs in the CNS, discuss several limitations to the eradication of brain reservoirs, and conclude the potential therapeutic implications of purging brain reservoirs.