JC virus induces altered patterns of cellular gene expression: Interferon-inducible genes as major transcriptional targets
JC virus induces altered patterns of cellular gene expression: Interferon-inducible genes as major transcriptional targets
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DOI：
10.1016/j.virol.2005.10.012
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发表时间：
2006-02-20
期刊：
影响因子：
3.7
通讯作者：
Nerurkar, VR
中科院分区：
文献类型：
--
作者：
Verma, S;Ziegler, K;Nerurkar, VR
人类多瘤病毒JC（JCV）感染了全球80%的人口。原发性感染通常发生在儿童时期，在免疫功能正常的个体中无症状，并导致终身潜伏和持续感染。然而，在严重的免疫功能低下，JCV可能会导致致命的脱髓鞘疾病，进行性多灶性白质脑病（PML）。影响持久性和致病性的病毒-宿主相互作用还不清楚，尽管认为JCV活性的显著调节发生在转录水平。在裂解周期中JCV早期和晚期启动子的调节是一个复杂的事件，需要病毒和细胞因子的参与。我们已经使用cDNA微阵列技术来分析在JCV允许的原代人胎儿神经胶质细胞（PHFG）的基因表达的全球变化。超过400个细胞基因的表达被改变，包括许多影响细胞增殖、细胞通讯和干扰素（IFN）介导的宿主防御反应的基因。后一类中的基因包括信号转导和转录激活因子1（STAT 1）、干扰素刺激基因56（ISG 56）、粘病毒抗性1（MxA）、2 '5'-寡腺苷酸合成酶（OAS）和cig 5。在JCV感染的PHFG细胞和人胶质母细胞瘤细胞系U87 MG中进一步证实了这些基因的表达，以确保JCV在诱导这种强抗病毒应答中的特异性。通过实时RT-PCR和Western印迹分析获得的结果支持了微阵列数据，并提供了与IFN应答途径中病毒诱导的变化相关的时间信息。我们的数据表明，诱导抗病毒反应可能是调节/控制免疫活性宿主中JCV复制的细胞因子之一，因此限制了PML的发展。(c)2005年爱思唯尔公司All rights reserved.
Human polyomavirus JC (JCV) infects 80% of the population worldwide. Primary infection, typically occurring during childhood, is asymptomatic in immunocompetent individuals, and results in lifelong latency and persistent infection. However, among the severely immunocompromised, JCV may cause a fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML). Virus-host interactions influencing persistence and pathogenicity are not well understood, although significant regulation of JCV activity is thought to occur at the level of transcription. Regulation of the JCV early and late promoters during the lytic cycle is a complex event that requires participation of both viral and cellular factors. We have used cDNA microarray technology to analyze global alterations in gene expression in JCV-permissive primary human fetal glial cells (PHFG). Expression of more than 400 cellular genes was altered, including many that influence cell proliferation, cell communication and interferon (1FN)-mediated host defense responses. Genes in the latter category included signal transducer and activator of transcription 1 (STAT1), interferon stimulating gene 56 (ISG56), myxovirus resistance 1 (MxA), 2'5'-oligoadenylate synthetase (OAS), and cig5. The expression of these genes was further confirmed in JCV-infected PHFG cells and the human glioblastoma cell line U87MG to ensure the specificity of JCV in inducing this strong antiviral response. Results obtained by real-time RT-PCR and Western blot analyses supported the microarray data and provide temporal information related to Virus-induced changes in the IFN response pathway. Our data indicate that the induction of an antiviral response may be one of the cellular factors regulating/controlling JCV replication in immunocompetent hosts and therefore constraining the development of PML. (c) 2005 Elsevier Inc. All rights reserved.