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Therapeutic potential of EBV infection

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Science Signaling  02 Jun 2020:
Vol. 13, Issue 634, eabd0677
DOI: 10.1126/scisignal.abd0677

Targeting MYC or factors that sustain its expression may turn EBV infection into a therapeutic tool for B cell lymphomas.

Harnessing oncolytic viruses has the potential to selectively kill tumors in patients by triggering antitumor immune responses. Latent, rather than lytic, phase Epstein-Barr virus (EBV), which exists as persistent infections in most of the world’s population, is associated with Burkitt’s and Hodgkin’s lymphomas, as well as various epithelial cancers. However, lytic—not latent—phase EBV antigens are immunogenic. Using a genome-wide, CRISPR/Cas9 loss-of-function screen, Guo et al. found that the transcription factor MYC was critical to maintaining EBV latency within Burkitt lymphoma cells. MYC, the abundance of which was supported by various epigenetic proteins, bound to promoters and remodeled chromatin to suppress myriad lytic-associated genes. Decreasing the expression of MYC directly or indirectly, such as by targeting one of the associated factors called FACT (facilitated chromatin transcription complex) with the small-molecule inhibitor CBL0137, reactivated the expression of many of the lytic genes in culture and in vivo. Given that EBV rapidly induces MYC expression in B cells upon infection, and that MYC drives the aggressive growth of B cell lymphomas, these findings suggest that reducing MYC expression in B cells, such as with CBL0137, may exploit EBV for therapeutic purposes, to enhance current or enable new treatment strategies in patients with EBV-positive B cell malignancies.

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