Reovirus-induced alteration in expression of apoptosis and DNA repair genes with potential roles in viral pathogenesis
Reovirus-induced alteration in expression of apoptosis and DNA repair genes with potential roles in viral pathogenesis
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DOI：
10.1128/jvi.77.16.8934-8947.2003
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发表时间：
2003-08-01
影响因子：
5.4
通讯作者：
Tyler, KL
中科院分区：
文献类型：
--
作者：
DeBiasi, RL;Clarke, P;Tyler, KL
呼肠孤病毒是理解病毒诱导的细胞凋亡的细胞机制的主要模型。呼肠孤病毒在体外可诱导多种细胞凋亡，而细胞凋亡在体内病毒诱导的心、脑组织损伤中起关键作用。转录因子NF-κ B和c-Jun的激活是呼肠孤病毒诱导细胞凋亡的关键事件，表明新基因的表达对这一过程至关重要。我们使用高密度寡核苷酸微阵列来分析用呼肠孤病毒株T3 A感染后HEK 293细胞中的细胞转录改变（即，凋亡诱导）与用呼肠孤病毒株T1 L感染（即，最低程度的凋亡诱导）和未感染的细胞。这些菌株在体内诱导感染小鼠心脏凋亡损伤的潜力也有显着差异-T3 A是心肌炎性的，而T1 L不是。使用超过12，000个基因的高通量微阵列分析，我们确定了呼肠孤病毒感染后参与细胞凋亡和DNA修复的基因的定义子集的差异表达。这提供了第一个比较分析不同凋亡表型的病毒感染后改变的基因表达，并提供了深入了解病毒诱导的疾病的致病机制。
Reoviruses are a leading model for understanding cellular mechanisms of virus-induced apoptosis. Reoviruses induce apoptosis in multiple cell lines in vitro, and apoptosis plays a key role in virus-induced tissue injury of the heart and brain in vivo. The activation of transcription factors NF-kappaB and c-Jun are key events in reovirus-induced apoptosis, indicating that new gene expression is critical to this process. We used high-density oligonucleotide microarrays to analyze cellular transcriptional alterations in HEK293 cells after infection with reovirus strain T3A (i.e., apoptosis inducing) compared to infection with reovirus strain T1L (i.e., minimally apoptosis inducing) and uninfected cells. These strains also differ dramatically in their potential to induce apoptotic injury in hearts of infected mice in vivo-T3A is myocarditic, whereas T1L is not. Using high-throughput microarray analysis of over 12,000 genes, we identified differential expression of a defined subset of genes involved in apoptosis and DNA repair after reovirus infection. This provides the first comparative analysis of altered gene expression after infection with viruses of differing apoptotic phenotypes and provides insight into pathogenic mechanisms of virus-induced disease.