...
首页> 外文期刊>Cell cycle >The Epstein-Barr virus replication and transcription activator, Rta/BRLF1, induces cellular senescence in epithelial cells.
【24h】

The Epstein-Barr virus replication and transcription activator, Rta/BRLF1, induces cellular senescence in epithelial cells.

机译:爱泼斯坦-巴尔病毒复制和转录激活剂Rta / BRLF1诱导上皮细胞衰老。

获取原文
获取原文并翻译 | 示例
           

摘要

Epstein-Barr Virus (EBV) replication and transcription activator (Rta/BRLF1) is an immediate-early transcription factor that controls the conversion of the latent viral genome into one undergoing lytic replication. By using a doxycycline-inducible expression system, the present study demonstrates that EBV Rta efficiently elicits growth arrest in the human epithelial cell line HEK293. In cells arrested by EBV Rta, the expression of p21 (CDKN1A), p27 (CDKN1B) and cyclin E were increased. In contrast, the levels of cyclin D1, CDK4 and CDK6 were sharply decreased. Activation of the host cell DNA damage response (DDR), indicated by the increasing phosphorylation of H2AX and p53 Ser15, was observed on day 3 and day 5 after EBV Rta expression, respectively. Finally, EBV Rta arrested cells exhibited strong senescence-associated beta-galactosidase staining on day 10 after doxycycline induction. Together, these results indicate that, in addition to triggering viral lytic replication in epithelial cells, EBV Rta concurrently initiates a cellular senescence program that was previously undocumented. This finding, showing Rta may be centrally involved in inducing a host cell state amenable to efficient viral reproduction, in addition to its previously characterized regulation of viral transcription, provides new perspectives in understanding EBV pathogenesis.
机译:爱泼斯坦-巴尔病毒(EBV)复制和转录激活因子(Rta / BRLF1)是一种早期转录因子,可控制潜在病毒基因组转化为裂解复制。通过使用强力霉素诱导的表达系统,本研究表明,EBV Rta可有效诱导人上皮细胞系HEK293的生长停滞。在被EBV Rta阻滞的细胞中,p21(CDKN1A),p27(CDKN1B)和细胞周期蛋白E的表达增加。相反,细胞周期蛋白D1,CDK4和CDK6的水平急剧下降。分别在EBV Rta表达后的第3天和第5天观察到H2AX和p53 Ser15磷酸化水平升高表明宿主细胞DNA损伤反应(DDR)激活。最后,在强力霉素被诱导后的第10天,EBV Rta被捕的细胞表现出强烈的衰老相关的β-半乳糖苷酶染色。总之,这些结果表明,除了在上皮细胞中触发病毒裂解复制外,EBV Rta同时启动了以前未记录的细胞衰老程序。这一发现表明Rta可能与诱导病毒有效转录的宿主细胞状态密切相关,除了它先前表征的病毒转录调控以外,还为理解EBV发病机理提供了新的见解。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号