Cross talk between EBV and telomerase: the role of TERT and NOTCH2 in the switch of latent/lytic cycle of the virus
S Giunco, A Celeghin, K Gianesin, R Dolcetti, S Indraccolo, A De Rossi
Cell Death and Disease | NATURE PUBLISHING GROUP | Published : 2015
Epstein-Barr virus (EBV)-associated malignancies, as well as lymphoblastoid cell lines (LCLs), obtained in vitro by EBV infection of B cells, express latent viral proteins and maintain their ability to grow indefinitely through inappropriate activation of telomere-specific reverse transcriptase (TERT), the catalytic component of telomerase. Our previous studies demonstrated that high levels of TERT expression in LCLs prevent the activation of EBV lytic cycle, which is instead triggered by TERT silencing. As lytic infection promotes the death of EBV-positive tumor cells, understanding the mechanism(s) by which TERT affects the latent/lytic status of EBV may be important for setting new therap..View full abstract
Awarded by Associazione Italiana per la Ricerca sul Cancro (AIRC)
We are very grateful to Jonas Ungerback (Linkopings University, Linkoping, Sweden) for the gift of the plasmids expressing luciferase under the control of larger (pGL3N2PR-2327/99) and smaller (pGL3N2PR-110) NOTCH2 promoters and the plasmid expressing an S33Y-mutated beta-catenin protein (pCGN-HA- S33Y-beta catenin), to Chantal Autexier (Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada) for the gift of the plasmid expressing human TERT linked to enhanced green fluorescent protein in pEGFP (pEGFP-hTERT) and the control vector pEGFP-C1, and to Adolfo Ferrando (Columbia University, New York, NY, USA) for the gift of plasmids expressing the intracellular domain of NOTCH2 (pMigRI-ICN2 and pMSCVpuro-ICN2). This study was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC Grant N 14258). SG is supported by a fellowship from AIRC.