Ahmed Waqar, Hassan Zubaida, Abdelmowla Yasmeen A A, Philip Pretty S, Shmygol Anatoliy, Khan Gulfaraz
Departments of Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
Departments of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
Virus Res. 2021 Nov;305:198550. doi: 10.1016/j.virusres.2021.198550. Epub 2021 Aug 27.
Epstein-Barr virus encoded RNAs (EBER1 and EBER2) are two non-polyadenylated, non-protein coding small RNAs expressed at high levels in all forms of EBV latent infections. Although not directly involved in cell transformation, a number of studies have reported that these RNAs may be involved in cell proliferation. However, which of the two EBERs play a major role in this process and the mechanisms involved remains unknown. The aim of this study was to investigate the role and mechanism of EBER1-induced cell proliferation. Using stably transfected EBER1 cell lines, and multiple methodologies, we show that EBER1 transfected epithelial, B and T cell lines proliferate at a higher rate, have higher metabolic activity and increased DNA synthesis. The mitochondrial number and activity was also observed to be higher in the EBER1 transfected cells. Moreover, cytochrome c activity and store operated calcium entry (SOCE) were potentiated in the EBER1 expressing cells. Finally, the genes associated with cell proliferation were also observed to be up-regulated in the EBER1 transfected cells. Taken together, our data has unravelled the role of mitochondria and cellular calcium pathway that appear to be involved in EBER1 induced cell proliferation of EBV infected cells.
爱泼斯坦-巴尔病毒编码的RNA（EBER1和EBER2）是两种非多聚腺苷酸化、非蛋白质编码的小RNA，在所有形式的EBV潜伏感染中均高水平表达。尽管不直接参与细胞转化，但多项研究报道这些RNA可能参与细胞增殖。然而，两种EBERs中哪一种在此过程中起主要作用以及涉及的机制仍不清楚。本研究的目的是探讨EBER1诱导细胞增殖的作用和机制。使用稳定转染EBER1的细胞系，并采用多种方法，我们发现转染EBER1的上皮细胞、B细胞和T细胞系增殖速率更高，具有更高的代谢活性且DNA合成增加。在转染EBER1的细胞中还观察到线粒体数量和活性更高。此外，在表达EBER1的细胞中，细胞色素c活性和储存性钙内流（SOCE）增强。最后，在转染EBER1的细胞中还观察到与细胞增殖相关的基因上调。综上所述，我们的数据揭示了线粒体和细胞钙途径在EBER1诱导的EBV感染细胞增殖中所起的作用。
