Coxsackievirus B3 infection induces cyr61 activation via JNK to mediate cell death
Coxsackievirus B3 infection induces cyr61 activation via JNK to mediate cell death
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DOI：
10.1128/jvi.78.24.13479-13488.2004
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发表时间：
2004-12-01
影响因子：
5.4
通讯作者：
Nam, JH
中科院分区：
文献类型：
--
作者：
Kim, SM;Park, JH;Nam, JH
柯萨奇病毒B3（CVB3）是小核糖核酸病毒科的一种肠道病毒，是与心肌炎和特发性扩张型心肌病相关的最常见的人类病原体。我们用cDNA微阵列方法发现了CVB 3感染HeLa细胞后富含半胱氨酸的蛋白基因（Cys 61）的上调，这一点通过北方印迹分析得到证实。结果表明，CVB3感染HeLa细胞后，细胞外Cyr61蛋白表达量增加。Cyr61是一种早期转录的基因，Cyr61蛋白被分泌到细胞外基质中。其功能与细胞粘附、迁移和神经元细胞死亡有关。在这里，我们表明，激活的CVB 3感染的JNK 61启动子是依赖于JNK激活诱导的CVB 3复制和病毒蛋白表达在感染的细胞。为了探索Cyr61蛋白在感染的HeLa细胞中的作用，我们瞬时过表达Cyr61并用CVB3感染HeLa细胞。这增加了CVB3在细胞中的生长，并促进了病毒感染引起的宿主细胞死亡，而用短干扰RNA下调C5761的表达降低了CVB3的生长，并显示出对CVB3感染引起的细胞死亡的抗性。总之，我们已经证明了一个新的作用，在HeLa细胞感染CVB3，这是与病毒感染诱导的细胞死亡。因此，这些数据扩展了我们对病毒诱导细胞死亡中的BMP61生理功能的理解，并为相关的细胞因子提供了新的见解。
Coxsackievirus B3 (CVB3), an enterovirus in the Picornavirus family, is the most common human pathogen associated with myocarditis and idiopathic dilated cardiomyopathy. We found upregulation of the cysteine-rich protein gene (cyr61) after CVB3 infection in HeLa cells with a cDNA microarray approach, which is confirmed by Northern blot analysis. It is also revealed that the extracellular amount of Cyr61 protein was increased after CVB3 infection in HeLa cells. cyr61 is an early-transcribed gene, and the Cyr61 protein is secreted into the extracellular matrix. Its function is related to cell adhesion, migration, and neuronal cell death. Here, we show that activation of the cyr61 promoter by CVB3 infection is dependent on JNK activation induced by CVB3 replication and viral protein expression in infected cells. To explore the role of Cyr61 protein in infected HeLa cells, we transiently overexpressed cyr61 and infected HeLa cells with CVB3. This increased CVB3 growth in the cells and promoted host cell death by viral infection, whereas down-expression of cyr61 with short interfering RNA reduced CVB3 growth and showed resistance to cell death by CVB3 infection. In conclusion, we have demonstrated a new role for cyr61 in HeLa cells infected with CVB3, which is associated with the cell death induced by virus infection. These data thus expand our understanding of the physiological functions of cyr61 in virus-induced cell death and provide new insights into the cellular factors involved.