%0 Journal Article %1 GUO2020 %A Guo, Rui %A Jiang, Chang %A Zhang, Yuchen %A Govande, Apurva %A Trudeau, Stephen J. %A Chen, Fang %A Fry, Christopher J. %A Puri, Rishi %A Wolinsky, Emma %A Schineller, Molly %A Frost, Thomas C. %A Gebre, Makda %A Zhao, Bo %A Giulino-Roth, Lisa %A Doench, John G. %A Teng, Mingxiang %A Gewurz, Benjamin E. %D 2020 %J Molecular Cell %K b-cell epstein-barr herpesvirus lmp1 myown virus %R https://doi.org/10.1016/j.molcel.2020.03.025 %T MYC Controls the Epstein-Barr Virus Lytic Switch %U http://www.sciencedirect.com/science/article/pii/S1097276520301933 %X Summary 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.

@article{GUO2020, abstract = {Summary 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.}, added-at = {2020-04-24T04:24:56.000+0200}, author = {Guo, Rui and Jiang, Chang and Zhang, Yuchen and Govande, Apurva and Trudeau, Stephen J. and Chen, Fang and Fry, Christopher J. and Puri, Rishi and Wolinsky, Emma and Schineller, Molly and Frost, Thomas C. and Gebre, Makda and Zhao, Bo and Giulino-Roth, Lisa and Doench, John G. and Teng, Mingxiang and Gewurz, Benjamin E.}, biburl = {https://www.bibsonomy.org/bibtex/21da004d530a281c61dc72a261e90c6c7/bgewurz}, doi = {https://doi.org/10.1016/j.molcel.2020.03.025}, interhash = {9def3881bb75b7328e236c09d750cadd}, intrahash = {1da004d530a281c61dc72a261e90c6c7}, issn = {1097-2765}, journal = {Molecular Cell}, keywords = {b-cell epstein-barr herpesvirus lmp1 myown virus}, timestamp = {2020-04-28T23:54:50.000+0200}, title = {MYC Controls the Epstein-Barr Virus Lytic Switch}, url = {http://www.sciencedirect.com/science/article/pii/S1097276520301933}, year = 2020 }