EGR1 upregulation following Venezuelan equine encephalitis virus infection is regulated by ERK and PERK pathways contributing to cell death
EGR1 upregulation following Venezuelan equine encephalitis virus infection is regulated by ERK and PERK pathways contributing to cell death
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DOI：
10.1016/j.virol.2019.10.016
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发表时间：
2020-01-02
期刊：
影响因子：
3.7
通讯作者：
Kehn-Hall, Kylene
中科院分区：
文献类型：
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作者：
Dahal, Bibha;Lin, Shih-Chao;Kehn-Hall, Kylene
委内瑞拉马脑炎病毒（VEEV）是一种嗜神经病毒，可在人和马中引起重大疾病。在这里，我们描述了VEEV对人类原代星形胶质细胞中调节细胞死亡的信号通路的影响。VEEV可有效感染原代星形胶质细胞，并在感染后9和18 h引起早期生长反应1 （EGR1）基因表达上调。EGR1的诱导依赖于细胞外信号调节的激酶1/2 （ERK1/2）和蛋白激酶R （PKR）样内质网激酶（PERK），而不依赖于p38丝裂原激活的蛋白激酶（MAPK）或磷酸肌肽3激酶（PI3K）信号。EGR1敲低可显著降低veev诱导的细胞凋亡，影响病毒复制。敲低ERK1/2或PERK可显著降低EGR1基因表达，显著减少病毒复制，提高细胞存活率，并挽救veev诱导的细胞凋亡。这些数据表明，在VEEV感染的原代星形胶质细胞中，EGR1的激活和随后的细胞死亡是通过ERK和PERK途径调控的。
Venezuelan equine encephalitis virus (VEEV) is a neurotropic virus that causes significant disease in both humans and equines. Here we characterized the impact of VEEV on signaling pathways regulating cell death in human primary astrocytes. VEEV productively infected primary astrocytes and caused an upregulation of early growth response 1 (EGR1) gene expression at 9 and 18 h post infection. EGR1 induction was dependent on extracellular signal-regulated kinase1/2 (ERK1/2) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), but not on p38 mitogen activated protein kinase (MAPK) or phosphoinositide 3-kinase (PI3K) signaling. Knockdown of EGR1 significantly reduced VEEV-induced apoptosis and impacted viral replication. Knockdown of ERK1/2 or PERK significantly reduced EGR1 gene expression, dramatically reduced viral replication, and increased cell survival as well as rescued cells from VEEV-induced apoptosis. These data indicate that EGR1 activation and subsequent cell death are regulated through ERK and PERK pathways in VEEV infected primary astrocytes.