Abstract
BackgroundLittle is known about the physiological role of the EBER1 and 2 nuclear RNAs during Epstein Barr viral infection. The EBERs are transcribed by cellular RNA Polymerase III and their strong expression results in 106 to 107 copies per EBV infected cell, making them reliable diagnostic markers for the presence of EBV. Although the functions of most of the proteins targeted by EBER RNAs have been studied, the role of EBERs themselves still remains elusive.FindingsThe cellular transcription response to EBER2 expression using the wild-type and an internal deletion mutant was determined. Significant changes in gene expression patterns were observed. A functional meta-analysis of the regulated genes points to inhibition of stress and immune responses, as well as activation of cellular growth and cytoskeletal reorganization as potential targets for EBER2 RNA. Different functions can be assigned to different parts of the RNA.ConclusionThese results provide new avenues to the understanding of EBER2 and EBV biology, and set the grounds for a more in depth functional analysis of EBER2 using transcriptome activity measurements.
Highlights
Little is known about the physiological role of the EBER1 and 2 nuclear RNAs during Epstein Barr viral infection
The EBERs are transcribed by cellular RNA Polymerase III and their strong expression results in 106 to 107 copies per EBV infected cell [8,9], making them reliable diagnostic markers for the presence of EBV
The two alternate EBER2-L2 structures differ in their free energy by 3.1 kJ, and retain the entire 5'3' stem structure (S) as well as the entire or the upper part of the loop 1 (L1)
Summary
Epstein-Barr virus (EBV) is a member of the herpesvirus family present in almost the entire human adult population [1,2,3] and has been found to be associated with oncogenesis of Burkitt's lymphoma, B- and T-cell leukemia/ lymphomas, nasopharyngeal carcinoma, breast cancer and gastric cancer [4,5,6,7]. In EBV infected cells, several viral genes are expressed of which the six nuclear antigens (EBNAs 1–6), the three membrane proteins (LMP-1, -2A and -2B) and the small non translated EBER1 and EBER2 RNAs are the most abundant [1,3]. A recent report indicates that rather EBER2 than EBER1 plays a central role in B-cell growth transformation [22]. Given this indication of a transcriptional response to EBER expression, as well as the indication of the functional implication of EBER2 in cellular transformation, we used microarrays to assess transcriptome changes following expression of EBER2 in HEK 293 cells
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