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.
Pubmed ID: 32315601 RIS Download
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A multiple sequence alignment server which can align Protein, DNA and RNA sequences.
View all literature mentionsSoftware package for differential gene expression analysis based on the negative binomial distribution. Used for analyzing RNA-seq data for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.
View all literature mentionsProvides bioinformatics services to research groups in Babraham Institute, United Kingdom and external commercial consultancy service. Provides assistance in genomics, proteomics, statistics, microarrays, and custom software development.
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View all literature mentionsThis monoclonal targets GCN5L2
View all literature mentionsThis polyclonal targets TADA2B
View all literature mentionsThis monoclonal targets GAPDH
View all literature mentionsThis monoclonal targets EBV ZEBRA (BZ1)
View all literature mentionsThis monoclonal targets Myc
View all literature mentionsThis polyclonal targets MYC
View all literature mentionsThis monoclonal targets c-Myc
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis isotype control targets not applicable
View all literature mentionsThis polyclonal targets Gcn5
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Daudi is a Cancer cell line with a species of origin Homo sapiens (Human)
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Mus musculus with name NOD.Cg-Prkdcscid Il2rg