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Expression of Rta in B Lymphocytes during Epstein-Barr Virus Latency.
Journal of Molecular Biology ( IF 4.7 ) Pub Date : 2020-07-23 , DOI: 10.1016/j.jmb.2020.07.011
Sseu-Pei Hwang,Lin-Chen Huang,Wen-Hung Wang,Min-Hsuan Lin,Chung-Wen Kuo,Hsiang-Hung Huang,Li-Kwan Chang

Rta of Epstein–Barr virus (EBV) is thought to be expressed only during the lytic cycle to promote the transcription of lytic genes. However, we found that Rta is expressed in EBV-infected B cells during viral latency, at levels detectable by immunoblot analysis. Latent Rta expression cannot be attributed to spontaneous lytic activation, as we observed that more than 90% of Akata, P3HR1, and 721 cells latently infected by EBV express Rta. We further found that Rta is sequestered in the nucleolus during EBV latency through its interaction with MCRS2, a nucleolar protein. When Rta is sequestered in the nucleolus, it no longer activates RNA polymerase II-driven transcription, thus explaining why Rta expression during latency does not transactivate EBV lytic genes. Additional experiments showed that Rta can bind to 18S rRNA and become incorporated into ribosomes, and a transient transfection experiment showed that Rta promotes translation from an mRNA reporter. These findings reveal that Rta has novel functions beyond transcriptional activation during EBV latency and may have interesting implications for the concept of EBV latency.



中文翻译:

EB病毒潜伏期期间B淋巴细胞中Rta的表达。

据认为,爱泼斯坦-巴尔病毒(EBV)的Rta仅在裂解循环中表达,以促进裂解基因的转录。但是,我们发现Rta在病毒潜伏期中被EBV感染的B细胞表达,其水平可通过免疫印迹分析检测到。潜在的Rta表达不能归因于自发的裂解激活,因为我们观察到90%的被EBV潜在感染的Akata,P3HR1和721细胞表达Rta。我们进一步发现,Rta通过其与核仁蛋白MCRS2的相互作用而被隔离在EBV潜伏期的核仁中。当Rta被隔离在核仁中时,它不再激活RNA聚合酶II驱动的转录,从而解释了为什么在潜伏期Rta表达不能激活EBV裂解基因。其他实验表明Rta可以结合18S rRNA并整合入核糖体中,而瞬时转染实验表明Rta可以促进mRNA报告基因的翻译。这些发现表明,Rta在EBV潜伏期具有超越转录激活的新颖功能,并且可能对EBV潜伏期的概念产生有趣的影响。

更新日期:2020-09-16
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