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Expression profile of Epstein-Barr virus and human adenovirus small RNAs in tonsillar B and T lymphocytes
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN USA..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 5, e0177275Article in journal (Refereed) Published
Abstract [en]

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 A 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 A end but alternative 3 A ends. A range of small RNAs was also detected from the terminal stem of the EBER RNAs and the 3 A 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 A mivaRNA from VA RNAI and the 3 A mivaRNA from VA RNAII were as predicted, whereas the 3 A mivaRNA from VA RNAI showed an aberrant processing upstream of the expected Dicer cleavage site.

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PUBLIC LIBRARY SCIENCE , 2017. Vol. 12, no 5, e0177275
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Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-326234DOI: 10.1371/journal.pone.0177275ISI: 000402062800013PubMedID: 28542273OAI: oai:DiVA.org:uu-326234DiVA: diva2:1120432
Funder
Swedish Cancer Society, 120678, 130469
Available from: 2017-07-06 Created: 2017-07-06 Last updated: 2017-11-29Bibliographically approved

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