Epstein-Barr virus-encoded RNAs (EBERs) complement the loss of Herpesvirus telomerase RNA (vTR) in virus-induced tumor formation

Scientific Reports
Ahmed Kheimar, Benedikt B Kaufer

Abstract

Marek's disease virus (MDV) is an alphaherpesvirus that causes fatal lymphomas in chickens and is used as a natural virus-host model for herpesvirus-induced tumorigenesis. MDV encodes a telomerase RNA subunit (vTR) that is crucial for efficient MDV-induced lymphoma formation; however, the mechanism is not completely understood. Similarly, Epstein Barr-virus (EBV) encodes two RNAs (EBER-1 and EBER-2) that are highly expressed in EBV-induced tumor cells, however their role in tumorigenesis remains unclear. Intriguingly, vTR and EBER-1 have interaction partners in common that are highly conserved in humans and chickens. Therefore, we investigated if EBER-1 and/or EBER-2 can complement the loss of vTR in MDV-induced tumor formation. We first deleted vTR (v∆vTR) and replaced it by either EBER-1 or EBER-2 in the very virulent RB-1B strain. Insertion of either EBER-1 or EBER-2 did not affect MDV replication and their expression levels were comparable to vTR in wild type virus. Intriguingly, EBER-2 restored tumor formation of MDV that lacks vTR. EBER-1 partially restored MDV oncogenicity, while tumor formation was severely impaired in chickens infected with v∆vTR. Our data provides the first evidence that EBERs possess tumor-promoting ...Continue Reading

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Citations

Aug 21, 2018·Annual Review of Pathology·Paul J Farrell
May 1, 2019·Annual Review of Virology·Johanna B WithersJoan A Steitz
Oct 11, 2019·MSphere·Andelé M ConradieBenedikt B Kaufer
Mar 14, 2020·Cancers·Luca D BertzbachBenedikt B Kaufer
Jul 8, 2020·Seminars in Cell & Developmental Biology·Takanobu TagawaJoseph Ziegelbauer
Feb 3, 2021·Cancer Treatment and Research Communications·Ali Salimi-JedaAsghar Abdoli
Aug 8, 2021·Cancers·Kin Israel NotartePaul Murray

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