التفاصيل البيبلوغرافية
| العنوان: |
MYC Controls the Epstein-Barr Virus Lytic Switch. |
| المؤلفون: |
Guo, Rui1,2,3 (AUTHOR), Jiang, Chang1,2,3 (AUTHOR), Zhang, Yuchen1,2,3,4 (AUTHOR), Govande, Apurva5 (AUTHOR), Trudeau, Stephen J.1,2,3 (AUTHOR), Chen, Fang6 (AUTHOR), Fry, Christopher J.6 (AUTHOR), Puri, Rishi7 (AUTHOR), Wolinsky, Emma1,2,3 (AUTHOR), Schineller, Molly1,2,3 (AUTHOR), Frost, Thomas C.5 (AUTHOR), Gebre, Makda5 (AUTHOR), Zhao, Bo1 (AUTHOR), Giulino-Roth, Lisa8 (AUTHOR), Doench, John G.3 (AUTHOR), Teng, Mingxiang1,9 (AUTHOR) mingxiang.teng@moffitt.org, Gewurz, Benjamin E.1,2,3,5 (AUTHOR) bgewurz@bwh.harvard.edu |
| المصدر: |
Molecular Cell. May2020, Vol. 78 Issue 4, p653-653. 1p. |
| مصطلحات موضوعية: |
*EPSTEIN-Barr virus, *B cell lymphoma, *LYTIC cycle, *VIRAL antigens, *LYMPHOPROLIFERATIVE disorders, *PLASMA cells |
| مستخلص: |
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. • CRISPR/Cas9 screen highlights host epigenetic suppressors of the EBV lytic cycle • EBV senses MYC abundance to maintain B cell latency • MYC depletion alters three-dimensional EBV genomic architecture • FACT is a druggable target for Burkitt B cell EBV latency reversal Epstein-Barr virus-infected Burkitt lymphomas evade immune detection by silencing all but one viral latency protein. Guo and Jiang et al. utilize a CRISPR screen to identify MYC as a key suppressor of nearly 80 viral lytic antigens. MYC depletion causes three-dimensional viral genome remodeling, suggesting a sensor mechanism and therapeutic approaches. [ABSTRACT FROM AUTHOR] |
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