Mankowski Joseph L, Clements Janice E, Zink M Christine
Department of Comparative Medicine, Johns Hopkins Medical Institutions, 600 N. Wolfe Street, Baltimore, MD 21287-7609, USA.
J Infect Dis. 2002 Dec 1;186 Suppl 2:S199-208. doi: 10.1086/344938.
An accelerated model of human immunodeficiency virus central nervous system disease was developed in which more than 90% of infected macaques develop typical simian immunodeficiency virus (SIV) encephalitis with neuronal dysfunction by postinoculation (pi) day 84. Infected macaques had replicating virus and microglial activation in the brain 10 days after inoculation; viral replication and microglial activation were suppressed at pi day 21. By pi day 56, viral recrudescence in the brain was detected in 2 of 6 infected macaques. CD4 cells were the predominant lymphocytes in the brain during acute and asymptomatic infection; cytotoxic T lymphocytes and NK cells predominated in macaques with encephalitis. Low levels of peripheral blood NK lytic activity at pi day 10, elevated cerebrospinal fluid (CSF) monocyte chemoattractant protein-1 after 28 days, and high CSF viral RNA after 42 days predicted SIV encephalitis. This model is ideal to track the viral, cellular, and immunologic changes in the brain during acute and asymptomatic infection and during viral recrudescence and SIV encephalitis.
构建了一种人类免疫缺陷病毒中枢神经系统疾病的加速模型，在该模型中，超过90%的受感染猕猴在接种后第84天出现典型的猿猴免疫缺陷病毒（SIV）脑炎并伴有神经元功能障碍。受感染的猕猴在接种后10天大脑中出现病毒复制和小胶质细胞激活；在接种后第21天病毒复制和小胶质细胞激活受到抑制。到接种后第56天，在6只受感染的猕猴中有2只检测到大脑中的病毒复发。在急性和无症状感染期间，CD4细胞是大脑中主要的淋巴细胞；在患有脑炎的猕猴中，细胞毒性T淋巴细胞和NK细胞占主导地位。接种后第10天外周血NK细胞溶解活性低、28天后脑脊液（CSF）单核细胞趋化蛋白-1升高以及42天后脑脊液病毒RNA高可预测SIV脑炎。该模型非常适合追踪急性和无症状感染期间以及病毒复发和SIV脑炎期间大脑中的病毒、细胞和免疫学变化。
