Differential apoptotic signaling in primary glial cells infected with herpes simplex virus 1
Differential apoptotic signaling in primary glial cells infected with herpes simplex virus 1
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DOI：
10.1080/13550280601064921
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发表时间：
2006-12-01
影响因子：
3.2
通讯作者：
Lokensgard, James R.
中科院分区：
文献类型：
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作者：
Aravalli, Rajagopal N.;Hu, Shuxian;Lokensgard, James R.
小胶质细胞和星形胶质细胞是执行不同功能并产生先天免疫应答以对抗入侵病原体的胶质细胞类型。单纯疱疹病毒1型（HSV-1）是一种嗜神经病毒，能够引起严重的坏死性脑炎。HSV-1感染这两种神经胶质细胞类型。小胶质细胞经历失败的感染，但通过诱导促炎细胞因子和趋化因子的产生来响应病毒感染。在这种细胞因子爆发后，它们迅速屈服于细胞死亡。相比之下，星形胶质细胞确实允许生产性病毒复制，但不产生这些相同的先天免疫介质。虽然细胞凋亡已被牵连在一些急性和慢性神经系统疾病，很少有人知道病毒性脑炎期间的细胞凋亡。在本研究中，作者研究了HSV-1感染对细胞存活的影响，并研究了病毒感染的原代鼠神经胶质细胞的细胞死亡机制。作者报告说，虽然细胞凋亡在小胶质细胞中发生迅速，但在星形胶质细胞的生产性感染期间发生延迟。此外，微阵列研究揭示了这两种类型的神经胶质细胞之间的凋亡基因的表达的显着变化，表明在信号通路的关键差异。内源性以及外源性的凋亡途径被发现在这两种胶质细胞类型中被激活。具体而言，参与肿瘤坏死因子（TNF）信号通路的基因主要在小胶质细胞中上调，而Fas通路的基因在HSV感染星形胶质细胞期间被诱导。
Microglial cells and astrocytes are glial cell types that perform distinct functions and generate innate immune responses to counter invading pathogens. Herpes simplex virus 1 (HSV-1) is a neurotropic virus that is capable of causing severe, necrotizing encephalitis. HSV-1 infects both of these glial cell types. Microglial cells undergo an abortive infection, yet respond to viral infection by inducing a burst of proinflammatory cytokine and chemokine production. Following this cytokine burst, they rapidly succumb to cell death. In contrast, astrocytes do permit productive viral replication, but do not generate these same innate immune mediators. Although apoptosis has been implicated in a number of acute and chronic neurological disorders, little is known about apoptosis during viral encephalitis. In the present study, the authors investigated the effect of HSV-1 infection on cell survival and studied the mechanisms of cell-death in virus-infected, primary murine glial cells. The authors report that although apoptosis occurred rapidly in microglia, it was delayed during productive infection of astrocytes. Furthermore, microarray studies revealed significant variations in the expression of apoptotic genes between these two types of glial cells, indicating crucial differences in signaling pathways. Intrinsic as well as extrinsic pathways of apoptosis were found to be activated in both glial cell types. Specifically, genes involved in the tumor necrosis factor (TNF) signaling pathway were predominantly up-regulated in microglia, whereas genes of the Fas pathway were induced during HSV infection of astrocytes.