p53 Activation following Rift Valley Fever Virus Infection Contributes to Cell Death and Viral Production
p53 Activation following Rift Valley Fever Virus Infection Contributes to Cell Death and Viral Production
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DOI：
10.1371/journal.pone.0036327
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发表时间：
2012-05-04
期刊：
影响因子：
3.7
通讯作者：
Kehn-Hall, Kylene
中科院分区：
文献类型：
--
作者：
Austin, Dana;Baer, Alan;Kehn-Hall, Kylene
裂谷热病毒（RVFV）是一种新出现的病毒性人畜共患病，是造成牲畜毁灭性爆发的原因，并能在人类中引起潜在的致命疾病。研究表明，在感染后，某些病毒具有利用特定细胞信号传导途径来传播病毒感染的能力。p53的激活对于DNA损伤信号级联、细胞凋亡的启动、细胞周期停滞和多个基因的转录调节是重要的。目前的研究集中在RVFV感染和病毒复制中的p53信号转导的作用。这些结果显示在RVFV MP-12感染后，在几个丝氨酸位点处的p53磷酸化的上调高度依赖于病毒蛋白NS。qRT-PCR数据显示RVFV感染后参与细胞周期和凋亡调控的几个p53靶向基因的转录上调。细胞活力测定表明，p53的损失导致更少的RVFV诱导的细胞死亡。此外，在p53缺失细胞中降低的病毒滴度表明RVFV利用p53来增强病毒产生。总的来说，这些实验表明在RVFV感染期间利用p53信号传导途径诱导细胞死亡并增加病毒产生。
Rift Valley fever virus (RVFV) is an emerging viral zoonosis that is responsible for devastating outbreaks among livestock and is capable of causing potentially fatal disease in humans. Studies have shown that upon infection, certain viruses have the capability of utilizing particular cellular signaling pathways to propagate viral infection. Activation of p53 is important for the DNA damage signaling cascade, initiation of apoptosis, cell cycle arrest and transcriptional regulation of multiple genes. The current study focuses on the role of p53 signaling in RVFV infection and viral replication. These results show an up-regulation of p53 phosphorylation at several serine sites after RVFV MP-12 infection that is highly dependent on the viral protein NSs. qRT-PCR data showed a transcriptional up-regulation of several p53 targeted genes involved in cell cycle and apoptosis regulation following RVFV infection. Cell viability assays demonstrate that loss of p53 results in less RVFV induced cell death. Furthermore, decreased viral titers in p53 null cells indicate that RVFV utilizes p53 to enhance viral production. Collectively, these experiments indicate that the p53 signaling pathway is utilized during RVFV infection to induce cell death and increase viral production.