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 properties in vivo using this natural model for herpesvirus-
tumorigenesis.