HMS Virology

Virology Faculty Member - Benjamin Gewurz

Benjamin Gewurz

Assistant Professor of Medicine
Harvard Medical School, Brigham and Women's Hospital
Associate Head, Virology Program

Brigham and Women's Hospital
Channing Laboratory, Infectious Disease Lab
181 Longwood Ave.
Boston, MA 02115
Tel: 617-525-4282
Visit my lab page here.

EBV is an oncogenic gamma-herpesvirus that persistently infects >95% of adults worldwide. EBV causes infectious mononucleosis and human cancers. ~200,000 cancers are attributable to EBV each year worldwide. Intriguingly, these include lymphomas with distinct viral genome expression patterns: Burkitt lymphoma, Hodgkin lymphoma, HIV-associated lymphomas, post-transplant lymphomas and immune-senescence-associated lymphomas. EBV is also associated with epithelial malignancies, including nasopharyngeal and gastric carcinomas.  Our research focuses on how EBV reprograms key lymphocyte growth, survival, metabolic and immune-evasion pathways to enable persistent host infection, with the long-term goal of identifying targets for therapeutic intervention.

EBV’s association with cancer is an outgrowth of its relationship with host cells. Upon infection of primary B lymphocytes, EBV enters a state of viral latency, but is hardly quiescent. Rather, the EBV Latency III program expresses two membrane proteins, six nuclear factors and microRNAs to transform resting B-lymphocytes into rapidly growing lymphoblasts. EBV-infected cells enter germinal centers, where the viral genome expression pattern switches to the Latency II program. In Latency II, the viral membrane proteins LMP1 and LMP2A mimic CD40 and B-cell receptor signaling, and the genome-tethering factor EBNA1 is the only viral nuclear protein expressed.  As B-cells differentiate into memory cells, EBV switches to the Latency I state, where EBNA1 is the only viral protein expressed. This restricted viral latency state evades immune-detection. Host and viral factors that reprogram EBV latency states are incompletely understood.

Viral lytic replication is necessary for persistent host infection and for transmission between hosts.  Plasma cell differentiation triggers EBV lytic reactivation through incompletely defined mechanisms.
Current research includes:

CRISPR/Cas9 analysis of the EBV host/pathogen relationship.  We are using CRISPR genetic analysis to perform genome-wide screens and focused studies of host factors that control key stages of the EBV lifecycle. These include investigation of EBV-induced host dependency factors that enable transformed B-cell growth and survival, that reprogram EBV latency states, and that control the latency/lytic switch. We are also using CRISPR to identify mechanisms by which EBV evades key immune pathways, including subversion of the PDL1/PD1 T-cell immune checkpoint.
We are using multiplexed tandem-mass spectrometry to identify how EBV remodels the B-cell proteome during lytic versus latent B-cell infection. We are interested in defining EBV rewires host metabolic pathways to support lytic replication versus B-cell growth transformation.

Rare primary immunodeficiencies highlight mechanisms that control EBV and result in markedly elevated EBV viral loads and B-cell cancers. We are using immunologic and whole exome approaches to identify and characterize novel primary human immunodeficiency syndromes that result in the inability to control EBV infection.

Last Update: 5/20/2020


For a complete listing of publications click here.



Guo, R, Jiang, C, Zhang, Y, Govande, A, Wolinsky, E, Trudeau, SJ, Schineller, M, Liang, J, Frost, T, Gebre, M, Zhao, B, Giulino-Roth, L, Doench, JG, Teng, M and Gewurz, BE. MYC Controls the Epstein-Barr Virus Lytic Switch. Molecular Cell 2020. PMID: 32315601

Guo, R, Zhang,Y, Teng, M, Jiang, C, Schineller, M, Zhao, B, Doench, JG, O’Reilly, R, Cesarman, E, Giulino-Roth, L and Gewurz, BE. DNA Methylation Enzymes and PRC1 Restrict B-cell Epstein-Barr Virus Oncoprotein Expression. Nature Microbiology 2020. PMID: 32424339

Wang LW, Wang Z, Ersing I, Nobre L, Guo R, Jiang S, Trudeau S, Zhao B, Weekes MP, Gewurz BE. Epstein-Barr virus subverts mevalonate and fatty acid pathways to promote infected B-cell proliferation and survival. PLoS Pathog. 2019 Sep 13;15(9):e1008030. PMID: 31518366

Jiang C, Trudeau SJ, Cheong TC, Guo R, Teng M, Wang LW, Wang Z, Pighi C, Gautier-Courteille C, Ma Y, Jiang S, Wang C, Zhao B, Paillard L, Doench JG, Chiarle R, Gewurz BE. CRISPR/Cas9 Screens Reveal Multiple Layers of B cell CD40 Regulation. Cell Reports, 2019 Jul 30;28(5):1307-1322

Wang LW, Shen H, Nobre L, Ersing I, Paulo JA, Trudeau S, Wang Z, Smith NA, Ma Y, Reinstadler B, Nomburg J, Sommermann T, Cahir-McFarland E, Gygi SP, Mootha VK, Weekes MP, Gewurz BE. Epstein-Barr-Virus-Induced One-Carbon Metabolism Drives B Cell Transformation. Cell Metabolism, 2019

Gebre, M, Nomburg, JL and Gewurz, BE. CRISPR-Cas9 Genetic Analysis of Host-Virus Interactions.  Viruses, 2018 10(2):55.

Jiang S, Wang LW, Walsh MJ, Trudeau SJ, Gerdt C, Zhao B, Gewurz BE. CRISPR/Cas9-Mediated Genome Editing in Epstein-Barr Virus-Transformed Lymphoblastoid B-Cell Lines.  Curr Protoc Mol Biol. 2018 121:31.12.1-31

Wang LW, Trudeau SJ, Wang C, Gerdt C, Jiang S, Zhao B, Gewurz BE. Modulating Gene Expression in Epstein-Barr Virus (EBV)-Positive B Cell Lines with CRISPRa and CRISPRi. Curr Protoc Mol Biol. 2018 121:31.13.1-31.

Zhang H, Li Y, Wang HB, Zhang A, Chen ML, Fang ZX, Dong XD, Li SB, Du Y, Xiong D, He JY, Li MZ, Liu YM, Zhou AJ, Zhong Q, Zeng YX, Kieff E, Zhang Z, Gewurz BE, Zhao B, Zeng MS Ephrin receptor A2 is an epithelial cell receptor for Epstein-Barr virus entry Nat Microbiol. 2018 3(2):164-171

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