Analysis of the host transcriptome from demyelinating spinal cord of murine coronavirus-infected mice.
Analysis of the host transcriptome from demyelinating spinal cord of murine coronavirus-infected mice.
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DOI：
10.1371/journal.pone.0075346
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Weiss SR
中科院分区：
文献类型：
--
作者：
Elliott R;Li F;Dragomir I;Chua MM;Gregory BD;Weiss SR
小鼠肝炎病毒（MHV）持续感染小鼠中枢神经系统（CNS）会诱发病理上类似于多发性硬化症的脱髓鞘疾病，因此被用作模型系统。关于与 MHV 诱导的脱髓鞘相关并导致其发生的宿主因素的信息很少。在这里，我们详细介绍了与 MHV 诱导的脊髓脱髓鞘疾病相关的基因和途径。宿主转录组的高通量测序表明，脱髓鞘伴随着许多转录变化，表明免疫浸润以及细胞因子环境和脂质代谢的变化。我们发现证据表明，Th1 偏向的细胞因子/趋化因子反应和类二十烷酸衍生的炎症伴随着持续的 MHV 感染，并且抗原呈递正在进行。有趣的是，参与脂质运输、加工和分解代谢的基因表达增加，包括一些在神经退行性疾病中已知作用的基因，与脱髓鞘同时发生。最后，在持续感染的小鼠脊髓中，一些与破骨细胞或骨驻留巨噬细胞功能相关的基因（最显着的是 TREM2 和 DAP12）的表达上调。这项研究强调了伴随 MHV 诱导的脱髓鞘的宿主抗病毒反应的复杂性，并进一步支持了先前的发现，即 MHV 诱导的脱髓鞘是免疫介导的。有趣的是，这些数据表明破骨细胞的骨重吸收与骨骼和中枢神经系统中小胶质细胞的髓鞘碎片清除之间存在平行关系。据我们所知，这是第一份使用 RNA-seq 方法研究宿主中枢神经系统对持续性病毒感染的反应的报告。
Persistent infection of the mouse central nervous system (CNS) with mouse hepatitis virus (MHV) induces a demyelinating disease pathologically similar to multiple sclerosis and is therefore used as a model system. There is little information regarding the host factors that correlate with and contribute to MHV-induced demyelination. Here, we detail the genes and pathways associated with MHV-induced demyelinating disease in the spinal cord. High-throughput sequencing of the host transcriptome revealed that demyelination is accompanied by numerous transcriptional changes indicative of immune infiltration as well as changes in the cytokine milieu and lipid metabolism. We found evidence that a Th1-biased cytokine/chemokine response and eicosanoid-derived inflammation accompany persistent MHV infection and that antigen presentation is ongoing. Interestingly, increased expression of genes involved in lipid transport, processing, and catabolism, including some with known roles in neurodegenerative diseases, coincided with demyelination. Lastly, expression of several genes involved in osteoclast or bone-resident macrophage function, most notably TREM2 and DAP12, was upregulated in persistently infected mouse spinal cord. This study highlights the complexity of the host antiviral response, which accompany MHV-induced demyelination, and further supports previous findings that MHV-induced demyelination is immune-mediated. Interestingly, these data suggest a parallel between bone reabsorption by osteoclasts and myelin debris clearance by microglia in the bone and the CNS, respectively. To our knowledge, this is the first report of using an RNA-seq approach to study the host CNS response to persistent viral infection.
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DOI：
10.1016/j.bbadis.2010.07.008
发表时间：
2011-02
影响因子：
6.2
作者：
Chastain, Emily M. L.;Duncan, D'Anne S.;Rodgers, Jane M.;Miller, Stephen D.
通讯作者：
Miller, Stephen D.
影响因子：
30.8
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Crow, Yanick J.
影响因子：
15.3
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通讯作者：
Sinigaglia, F
影响因子：
3.7
作者：
CASTRO, RF;EVANS, GD;PERLMAN, S
通讯作者：
PERLMAN, S
影响因子：
4.4
作者：
Aoki, N;Kimura, S;Katagiri, M
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