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Epstein-Barr virus (EBV) causes endemic Burkitt lymphoma (BL) and immunosuppression-related lymphomas. These B cell malignancies arise by distinct transformation pathways and have divergent viral and host expression programs. To identify host dependency factors resulting from these EBV+, B cell-transformed cell states, we performed parallel genome-wide CRISPR/Cas9 loss-of-function screens in BL and lymphoblastoid cell lines (LCLs). These highlighted 57 BL and 87 LCL genes uniquely important for their growth and survival. LCL hits were enriched for EBV-induced genes, including viral super-enhancer targets. Our systematic approach uncovered key mechanisms by which EBV oncoproteins activate the PI3K/AKT pathway and evade tumor suppressor responses. LMP1-induced cFLIP was found to be critical for LCL defense against TNFα-mediated programmed cell death, whereas EBV-induced BATF/IRF4 were critical for BIM suppression and MYC induction in LCLs. Finally, EBV super-enhancer-targeted IRF2 protected LCLs against Blimp1-mediated tumor suppression. Our results identify viral transformation-driven synthetic lethal targets for therapeutic intervention.
Pubmed ID: 28494239 RIS Download
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Software package for high-performance read alignment, quantification and mutation discovery.General purpose read aligner which can be used to map both genomic DNA-seq reads and RNA-seq reads. Subread aligner as fast, accurate and scalable read mapping by seed-and-vote.These programs were also implemented in Bioconductor R package Rsubread.
View all literature mentionsOpen source software package for statistical programming language R to create plots based on grammar of graphics. Used for data visualization to break up graphs into semantic components such as scales and layers.
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 mentionsSoftware performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
View all literature mentionsSoftware performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
View all literature mentionsThis polyclonal targets EBNA 3A
View all literature mentionsThis unknown targets hTNFa-hIgG1 100 µg
View all literature mentionsThis monoclonal targets CD178
View all literature mentionsThis monoclonal targets CD71 (3B8 2A1)
View all literature mentionsThis polyclonal targets V5 Tag
View all literature mentionsThis monoclonal targets NF kappa B p52
View all literature mentionsThis polyclonal targets RELA
View all literature mentionsThis monoclonal targets NF-KappaB p65, phospho (Ser536)
View all literature mentionsThis monoclonal targets CD81
View all literature mentionsThis monoclonal targets CD19
View all literature mentionsThis monoclonal targets α-tubulin
View all literature mentionsThis monoclonal targets TNF-R1 (H-5)
View all literature mentionsThis monoclonal targets GAPDH
View all literature mentionsThis polyclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis monoclonal targets Glyceraldehyde-3-PDH (GAPDH)
View all literature mentionsThis unknown targets
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis monoclonal targets Phospho-Syk (Tyr525/526)
View all literature mentionsThis polyclonal targets IRF-4
View all literature mentionsThis monoclonal targets Bim (C34C5) Rabbit mAb
View all literature mentionsThis monoclonal targets BATF
View all literature mentionsThis monoclonal targets alpha Tubulin antibody [DM1A] - Loading Control
View all literature mentionsThis monoclonal targets Cleaved PARP (Asp214)
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)
View all literature mentionsA read summarization program, which counts mapped reads for the genomic features such as genes and exons.
View all literature mentionsSoftware package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on August 30,2023. Software for differential gene expression analysis based on the negative binomial distribution. It estimates variance-mean dependence in count data from high-throughput sequencing assays and tests for differential expression.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsThis unknown targets hTNFa-hIgG1 100 µg
View all literature mentionsThis monoclonal targets CD178
View all literature mentionsThis monoclonal targets CD71 (3B8 2A1)
View all literature mentionsThis polyclonal targets V5 Tag
View all literature mentionsThis monoclonal targets NF kappa B p52
View all literature mentionsThis polyclonal targets RELA
View all literature mentionsThis monoclonal targets NF-KappaB p65, phospho (Ser536)
View all literature mentionsThis monoclonal targets CD81
View all literature mentionsThis monoclonal targets CD19
View all literature mentionsThis monoclonal targets α-tubulin
View all literature mentionsThis monoclonal targets TNF-R1 (H-5)
View all literature mentionsThis monoclonal targets GAPDH
View all literature mentionsThis polyclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis monoclonal targets Glyceraldehyde-3-PDH (GAPDH)
View all literature mentionsThis unknown targets
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis monoclonal targets Phospho-Syk (Tyr525/526)
View all literature mentionsThis polyclonal targets IRF-4
View all literature mentionsThis monoclonal targets Bim (C34C5) Rabbit mAb
View all literature mentionsThis monoclonal targets BATF
View all literature mentionsThis monoclonal targets alpha Tubulin antibody [DM1A] - Loading Control
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