MYC Controls the Epstein-Barr Virus Lytic Switch.

Apr 22, 2020

Contributor: 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

MYC Controls the Epstein-Barr Virus Lytic Switch.

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.

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About The Expert

Rui Guo

Division of Infectious Disease, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

Chang Jiang

Division of Infectious Disease, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

Yuchen Zhang

Division of Infectious Disease, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Sun Yat-sen University Cancer Center, Guangzhou 510060, China.

Apurva Govande

Harvard Graduate Program in Virology, Boston, MA 02115, USA.

Stephen J Trudeau

Division of Infectious Disease, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

Fang Chen

Cell Signaling Technology, Inc., Danvers, MA 01923, USA.

Christopher J Fry

Cell Signaling Technology, Inc., Danvers, MA 01923, USA.

Rishi Puri

Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.

Emma Wolinsky

Division of Infectious Disease, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

Molly Schineller

Division of Infectious Disease, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

Thomas C Frost

Harvard Graduate Program in Virology, Boston, MA 02115, USA.

Makda Gebre

Harvard Graduate Program in Virology, Boston, MA 02115, USA.

Bo Zhao

Division of Infectious Disease, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

Lisa Giulino-Roth

Division of Pediatric Hematology/Oncology, Weill Cornell Medical College, New York, NY 10065, USA.

John G Doench

Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

Mingxiang Teng

Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA. Electronic address: mingxiang.teng@moffitt.org.

Benjamin E Gewurz

Division of Infectious Disease, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Harvard Graduate Program in Virology, Boston, MA 02115, USA. Electronic address: bgewurz@bwh.harvard.edu.

References

PubMed