Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
J Virol. 2013 Jun;87(11):6221-31. doi: 10.1128/JVI.00396-13. Epub 2013 Mar 27.
Viral infections of the central nervous system (CNS) are of increasing concern, especially among immunocompromised populations. Rodent models are often inappropriate for studies of CNS infection, as many viruses, including JC virus (JCV) and HIV, cannot replicate in rodent cells. Consequently, human fetal brain-derived multipotential CNS progenitor cells (NPCs) that can be differentiated into neurons, oligodendrocytes, or astrocytes have served as a model in CNS studies. NPCs can be nonproductively infected by JCV, while infection of progenitor-derived astrocytes (PDAs) is robust. We profiled cellular gene expression at multiple times during differentiation of NPCs to PDAs. Several activated transcription factors show commonality between cells of the brain, in which JCV replicates, and lymphocytes, in which JCV is likely latent. Bioinformatic analysis determined transcription factors that may influence the favorable transcriptional environment for JCV in PDAs. This study attempts to provide a framework for understanding the functional transcriptional profile necessary for productive JCV infection.
中枢神经系统（CNS）的病毒感染越来越受到关注，特别是在免疫功能低下的人群中。啮齿动物模型通常不适合用于 CNS 感染的研究，因为许多病毒，包括 JC 病毒（JCV）和 HIV，不能在啮齿动物细胞中复制。因此，能够分化为神经元、少突胶质细胞或星形胶质细胞的人胎脑来源多能性中枢神经系统祖细胞（NPC）已被用作 CNS 研究的模型。NPC 可以被 JCV 非生产性感染，而祖细胞衍生的星形胶质细胞（PDAs）的感染则很强烈。我们在 NPC 分化为 PDAs 的多个时间点对细胞基因表达进行了分析。几种激活的转录因子在 JCV 复制的脑细胞和 JCV 可能潜伏的淋巴细胞之间表现出共性。生物信息学分析确定了可能影响 PDAs 中 JCV 有利转录环境的转录因子。本研究试图为理解 JCV 生产性感染所需的功能转录谱提供一个框架。
