Gene expression in the brain during reovirus encephalitis.
Gene expression in the brain during reovirus encephalitis.
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DOI：
10.3109/13550280903586394
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发表时间：
2010-02
影响因子：
3.2
通讯作者：
Clarke P
中科院分区：
文献类型：
--
作者：
Tyler KL;Leser JS;Phang TL;Clarke P
病毒性脑炎仍然是全世界发病率和死亡率的一个重要原因。我们进行了微阵列分析，以确定呼肠孤病毒脑炎期间差异调节的基因和途径，并可能为病毒诱导的中枢神经系统（CNS）疾病提供新的治疗靶点。与模拟感染的对照组相比，在感染呼肠孤病毒的小鼠的大脑中，在感染后的早期发现了130个细胞基因的表达增加。这些基因的上调与先天免疫反应的激活一致，特别是干扰素信号。在感染后的后期，当存在显著的中枢神经系统损伤并且小鼠表现出严重神经系统疾病的迹象时，更多（1374）个基因被上调，表明基因表达增加与疾病病理相关。感染后后期病毒诱导的基因表达再次与先天免疫反应的激活一致。然而，其他重要的途径包括与细胞因子信号传导和细胞凋亡相关的途径，这两种途径都可能导致中枢神经系统损伤。这是第一份比较病毒感染大脑后早期和晚期病毒诱导的细胞基因和通路调控的报告。病毒诱导的基因表达从感染后早期的先天免疫反应转变为后期的细胞因子信号传导和细胞凋亡，这提示了一种潜在的治疗策略，即保留早期的保护反应，同时抑制导致发病的后期反应。
Viral encephalitis remains a significant cause of morbidity and mortality throughout the world. We performed microarray analysis to identify genes and pathways that are differentially regulated during reovirus encephalitis and that may provide novel therapeutic targets for virus-induced diseases of the central nervous system (CNS). An increase in the expression of 130 cellular genes was found in the brains of reovirus-infected mice at early times post infection, compared to mock-infected controls. The up-regulation of these genes was consistent with activation of innate immune responses, particularly interferon signaling. At later times post infection, when significant CNS injury is present and mice exhibit signs of severe neurologic disease, many more (1374) genes were up-regulated, indicating that increased gene expression correlates with disease pathology. Virus-induced gene expression at late times post infection was again consistent with the activation of innate immune responses. However, additional significant pathways included those associated with cytokine signaling and apoptosis, both of which can contribute to CNS injury. This is the first report comparing virus-induced cellular gene and pathway regulation at early and late times following virus infection of the brain. The shift of virus-induced gene expression from innate immune responses at early times post infection to cytokine signaling and apoptosis at later times suggests a potential therapeutic strategy that preserves early protective responses whilst inhibiting later responses that contribute to pathogenesis.
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影响因子：
5.4
作者：
DeBiasi, RL;Clarke, P;Tyler, KL
通讯作者：
Tyler, KL
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
56.9
作者：
MULLER, U;STEINHOFF, U;AGUET, M
通讯作者：
AGUET, M
影响因子：
4.8
作者：
Kajaste-Rudnitski, A;Mashimo, T;Desprès, P
通讯作者：
Desprès, P
影响因子：
5.4
作者：
Clarke, P;Meintzer, SM;Tyler, KL
通讯作者：
Tyler, KL