Anderson M G, Hauer D, Sharma D P, Joag S V, Narayan O, Zink M C, Clements J E
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Virology. 1993 Aug;195(2):616-26. doi: 10.1006/viro.1993.1413.
Nucleotide sequence analyses of the env genes of two neurotropic variants of SIVmac239 were performed to determine whether molecular changes in these genes could be correlated with neurotropism. Biological characterization of virus from the infectious molecular clone of SIVmac239 had shown that it is highly lymphocyte-tropic and poorly macrophage-tropic. This virus failed to replicate in the brain after intracerebral inoculation, but passage of this virus in macaques resulted in development of viral variants that had acquired cell tropism for macrophages and were neurovirulent (D. P. Sharma, M. C. Zink, H. Anderson, R. J. Adams, J. E. Clements, S. V. Joag, and O. Narayan, J. Virol., 66, 3550-3556, 1992). The neurotropic virus SIVmac239/R71 was obtained from the brain of a monkey after the third in vivo passage of SIVmac239. Inoculation of this virus into another macaque leads to CNS disease and the isolation of another neurotropic virus SIVmac239/17E. The viral env sequences obtained by polymerase chain reaction amplification directly from DNA obtained from the brain of R71 and 17E macaques had a limited number of changes dispersed throughout the env gene when compared to the parental virus, SIVmac239. The most important finding was that there was a common set of nucleotide changes in the env gene of both R71 and 17E. This suggested that viruses containing these changes had a selective growth advantage in the brain and were the predominant species present in the central nervous system of macaques R71 and 17E. Analysis of individual clones containing the R71 env gene revealed that different env genes were present, but all had the changes that were conserved in both R71 and 17E but not present in the original lymphocyte-tropic parental virus, SIVmac239. Construction of an infectious recombinant virus containing the tat, rev, and env genes from 17E and the remainder of the genome from the parental virus SIVmac239 resulted in a virus that had the macrophage-tropism of 17E virus isolated from brain. This demonstrates that the env gene of 17E confers the cellular tropism of the virus on the parental virus, SIVmac239.
对SIVmac239的两种嗜神经病毒变体的env基因进行了核苷酸序列分析，以确定这些基因中的分子变化是否与嗜神经性相关。来自SIVmac239感染性分子克隆的病毒的生物学特性表明，它具有高度嗜淋巴细胞性且嗜巨噬细胞性较差。这种病毒脑内接种后未能在脑中复制，但该病毒在猕猴体内传代导致了病毒变体的出现，这些变体获得了对巨噬细胞的细胞嗜性且具有神经毒性（D.P.沙尔马、M.C.津克、H.安德森、R.J.亚当斯、J.E.克莱门茨、S.V.乔格和O.纳拉扬，《病毒学杂志》，66，3550 - 3556，1992年）。嗜神经病毒SIVmac239/R71是在SIVmac239在体内第三次传代后从一只猴子的脑中获得的。将这种病毒接种到另一只猕猴体内会导致中枢神经系统疾病，并分离出另一种嗜神经病毒SIVmac239/17E。与亲本病毒SIVmac239相比，通过聚合酶链反应扩增直接从R71和17E猕猴脑内获得的DNA中得到的病毒env序列，在整个env基因中散布着数量有限的变化。最重要的发现是，R71和17E的env基因存在一组共同的核苷酸变化。这表明含有这些变化的病毒在脑中具有选择性生长优势，并且是R71和17E猕猴中枢神经系统中存在的主要病毒种类。对含有R71 env基因的单个克隆的分析表明，存在不同的env基因，但所有这些基因都具有在R71和17E中保守但在原始嗜淋巴细胞亲本病毒SIVmac239中不存在的变化。构建一种含有来自17E的tat、rev和env基因以及来自亲本病毒SIVmac239其余基因组的感染性重组病毒，产生了一种具有从脑中分离出的17E病毒巨噬细胞嗜性的病毒。这表明17E的env基因赋予了亲本病毒SIVmac239病毒的细胞嗜性。
