Epstein-Barr virus (EBV) is associated with multiple human malignancies. To evade immune detection, EBV switches between latent and lytic programs. How viral latency is maintained in tumors or in memory B cells, the reservoir for lifelong EBV infection, remains incompletely understood. To gain insights, we performed a human genome-wide CRISPR/Cas9 screen in Burkitt lymphoma B cells. Our analyses identified a network of host factors that repress lytic reactivation, centered on the transcription factor MYC, including cohesins, FACT, STAGA, and Mediator. Depletion of MYC or factors important for MYC expression reactivated the lytic cycle, including in Burkitt xenografts. MYC bound the EBV genome origin of lytic replication and suppressed its looping to the lytic cycle initiator BZLF1 promoter. Notably, MYC abundance decreases with plasma cell differentiation, a key lytic reactivation trigger. Our results suggest that EBV senses MYC abundance as a readout of B cell state and highlights Burkitt latency reversal therapeutic targets.Copyright © 2020 Elsevier Inc. All rights reserved.
About The Expert
Rui Guo
Chang Jiang
Yuchen Zhang
Apurva Govande
Stephen J Trudeau
Fang Chen
Christopher J Fry
Rishi Puri
Emma Wolinsky
Molly Schineller
Thomas C Frost
Makda Gebre
Bo Zhao
Lisa Giulino-Roth
John G Doench
Mingxiang Teng
Benjamin E Gewurz
References
PubMed
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