Expression profile of Epstein-Barr virus and human adenovirus small RNAs in tonsillar B and T lymphocytes

Farzaneh Assadian, Wael Kamel, Göran Laurell, Catharina Svensson, Tanel Punga, Göran Akusjärvi

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4 Scopus citations

Abstract

We have used high-throughput small RNA sequencing to characterize viral small RNA expression in purified tonsillar B and T lymphocytes isolated from patients tested positive for Epstein-Barr virus (EBV) or human adenovirus (HAdV) infections, respectively. In the small set of patients analyzed, the expression profile of EBV and HAdV miRNAs could not distinguish between patients diagnosed with tonsillar hypertrophy or chronic/recurrent tonsillitis. The EBV miR-BART expression profile among the patients diagnosed with tonsillar diseases resembles most closely the pattern seen in EBV+ tumors (Latency II/I). The miRBARTs that appear to be absent in normal EBV infected cells are essentially all detectable in the diseased tonsillar B lymphocytes. In the EBV+ B cells we detected 44 EBV miRBARTs derived from the proposed BART precursor hairpins whereof five are not annotated in miRBase v21. One previously undetected miRNA, BART16b-5p, originates from the miR-BART16 precursor hairpin as an alternative 5′ miR-BART16 located precisely upstream of the annotated miR-BART16-5p. Further, our analysis revealed an extensive sequence variation among the EBV miRNAs with isomiRs having a constant 5′ end but alternative 3′ ends. A range of small RNAs was also detected from the terminal stem of the EBER RNAs and the 3′ part of v-snoRNA1. During a lytic HAdV infection in established cell lines the terminal stem of the viral non-coding VA RNAs are processed to highly abundant viral miRNAs (mivaRNAs). In contrast, mivaRNA expression in HAdV positive tonsillar T lymphocytes was very low. The small RNA profile further showed that the 5′ mivaRNA from VA RNAI and the 3′ mivaRNA from VA RNAII were as predicted, whereas the 3′ mivaRNA from VA RNAI showed an aberrant processing upstream of the expected Dicer cleavage site.

Original languageEnglish (US)
Article numbere0177275
JournalPloS one
Volume12
Issue number5
DOIs
StatePublished - May 2017

Bibliographical note

Funding Information:
This work was supported by the Swedish Cancer Society (grant numbers 120678 and 130469, www.cancerfonden.se ) and the Swedish Research Council through a grant to the Uppsala RNA Research Centre (grant number 2006-5038-36531-16, www.vr.se ).

Publisher Copyright:
© 2017 Assadian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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