Gray Lachlan R, Brew Bruce J, Churchill Melissa J
aCenter for Biomedical Research, Burnet Institute bDepartment of Infectious Diseases, Monash University, Melbourne, Victoria cDepartments of Neurology, Immunology and Infectious Diseases and Peter Duncan Neurosciences Unit, St Vincent's Centre for Applied Medical Research, St Vincent's Hospital, Sydney, New South Wales dDepartment of Microbiology, Monash University, Clayton, Victoria eDepartment of Medicine, Monash University, Melbourne, Victoria, Australia.
Curr Opin HIV AIDS. 2016 Jul;11(4):371-5. doi: 10.1097/COH.0000000000000278.
To review current knowledge of viral reservoirs in the central nervous system (CNS) and identify the CNS-specific barriers and strategies to cure human immunodeficiency virus type 1 (HIV-1) within the brain.
The cumulative data of HIV-1 infection of the CNS support the ability of the CNS to act as a viral reservoir for HIV-1. The HIV-1 viral strains found in the CNS are distinct to those found in other parts of the body. These differences have been well documented for env and also extend to the viral promoter, the long terminal repeat, and influence the ability of the virus to replicate, establish latency and respond to latency-reversing agents (LRAs). In addition, the bioavailability and activity of LRAs and antiretrovirals within the CNS suggest altered properties compared with the blood, which may influence their effectiveness. Selected LRAs were shown to have reduced effectiveness against CNS-derived viral strains compared with blood-derived strains from the same patients. Finally, altered immune surveillance within the CNS may also interfere with the efficiency of cure strategies within this compartment.
Together, these data suggest that the CNS viral reservoir is unique and presents a distinct set of challenges that need to be overcome to ensure successful viral elimination within this compartment. Future studies will need to develop CNS-active LRAs and biomarkers to enable monitoring and evaluation of treatment outcomes within the CNS during HIV-1 cure clinical trials.
回顾目前关于中枢神经系统（CNS）中病毒储存库的知识，并确定中枢神经系统特异性障碍以及治愈脑内1型人类免疫缺陷病毒（HIV-1）的策略。
HIV-1感染中枢神经系统的累积数据支持中枢神经系统作为HIV-1病毒储存库的能力。在中枢神经系统中发现的HIV-1病毒株与在身体其他部位发现的病毒株不同。这些差异在env基因方面已有充分记录，并且还扩展到病毒启动子、长末端重复序列，并影响病毒复制、建立潜伏状态以及对潜伏逆转剂（LRA）作出反应的能力。此外，与血液相比，LRA和抗逆转录病毒药物在中枢神经系统中的生物利用度和活性表明其性质发生了改变，这可能会影响它们的有效性。与同一患者血液来源的病毒株相比，选定的LRA对中枢神经系统来源的病毒株显示出较低的有效性。最后，中枢神经系统内改变的免疫监视也可能干扰该区域内治愈策略的效率。
总之，这些数据表明中枢神经系统病毒储存库是独特的，并且提出了一系列独特的挑战，要确保在该区域成功清除病毒就需要克服这些挑战。未来的研究将需要开发具有中枢神经系统活性的LRA和生物标志物，以便在HIV-1治愈临床试验期间能够监测和评估中枢神经系统内的治疗结果。
