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 (vΔvTR) 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 vΔvTR. Our data provides the first evidence
that EBERs possess tumor-promoting properties in vivo using this natural model
for herpesvirustumorigenesis