Lane T E, Buchmeier M J, Watry D D, Jakubowski D B, Fox H S
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA.
Virology. 1995 Oct 1;212(2):458-65. doi: 10.1006/viro.1995.1503.
The pathogenic effects of HIV include infection of the central nervous system (CNS) which can result in cognitive and motor dysfunction. Simian immunodeficiency virus (SIV) infection of rhesus macaques provides an excellent model of HIV-induced disease. We have achieved a reproducible infection of the CNS using a stock of virus obtained by serial passage of microglia-associated SIV. Since the envelope genes of both HIV and SIV encode determinants important in viral pathogenesis, and the variability inherent in these viruses provides a molecular footprint of viral quasispecies, we analyzed the viral env sequences resulting from this serial passage. SIV env sequences were analyzed by direct PCR amplification of DNA isolated from microglia from infected animals. Nucleotide sequence comparison reveals that serial passage of microglia-associated SIV resulted in divergence from the donor stock of virus. Furthermore, an enrichment of unique env quasispecies which is maintained through the serial passage was found in the diseased brains.
人类免疫缺陷病毒(HIV)的致病作用包括感染中枢神经系统(CNS),这可导致认知和运动功能障碍。恒河猴感染猿猴免疫缺陷病毒(SIV)为HIV引发的疾病提供了一个极佳的模型。我们利用通过小胶质细胞相关SIV连续传代获得的一批病毒,实现了对中枢神经系统的可重复性感染。由于HIV和SIV的包膜基因都编码在病毒发病机制中起重要作用的决定簇,并且这些病毒固有的变异性提供了病毒准种的分子印记,因此我们分析了这种连续传代产生的病毒env序列。通过直接PCR扩增从感染动物的小胶质细胞中分离的DNA来分析SIV env序列。核苷酸序列比较显示,小胶质细胞相关SIV的连续传代导致与病毒供体毒株出现分歧。此外,在患病大脑中发现了通过连续传代得以维持的独特env准种的富集。