Limoges J, Poluektova L, Ratanasuwan W, Rasmussen J, Zelivyanskaya M, McClernon D R, Lanier E R, Gendelman H E, Persidsky Y
Department of Internal Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198-5215, USA.
Virology. 2001 Mar 1;281(1):21-34. doi: 10.1006/viro.2000.0758.
Development of anti-retroviral regimens with enhanced efficacy against brain HIV-1 is essential if viral eradication is to be achieved. To address this, a severe combined immune deficiency mouse model of HIV-1 encephalitis was used to assay the effect of protease-containing and protease-sparing drug regimens on viral replication in brain macrophages. Here, HIV-1-infected human monocyte-derived macrophages (MDM) are inoculated into basal ganglia, causing a multinucleated giant cell encephalitis reminiscent of human disease. Drugs were administered at the time of MDM inoculation and continued until sacrifice. Immunohistochemical tests evaluated ongoing viral replication, glial immunity, and neuronal survival. Treatment with ddI/d4T decreased the numbers of infected cells by 75%, while ddI/d4T/amprenavir or ZDV/3TC/ABC diminished infection by 98%. Triple drug regimens decreased astrogliosis by > or = 25%. This small-animal model may be used to screen drug regimens that affect ongoing HIV-1 replication within its brain sanctuary.
如果要实现病毒根除，开发出对脑内HIV-1具有更高疗效的抗逆转录病毒治疗方案至关重要。为解决这一问题，利用HIV-1脑炎的严重联合免疫缺陷小鼠模型来测定含蛋白酶和不含蛋白酶的药物治疗方案对脑巨噬细胞中病毒复制的影响。在此，将感染HIV-1的人单核细胞衍生巨噬细胞（MDM）接种到基底神经节，引发类似于人类疾病的多核巨细胞脑炎。在接种MDM时给药，并持续至处死。免疫组织化学检测评估了正在进行的病毒复制、神经胶质免疫和神经元存活情况。用ddI/d4T治疗使感染细胞数量减少了75%，而ddI/d4T/安普那韦或齐多夫定/拉米夫定/阿巴卡韦使感染减少了98%。三联药物治疗方案使星形胶质细胞增生减少了≥25%。这个小动物模型可用于筛选影响脑内HIV-1病毒库中正在进行的病毒复制的药物治疗方案。
