Kaposi’s Sarcoma-Associated Herpesvirus Drives a Super-Enhancer-Mediated Survival Gene Expression Program in Primary Effusion Lymphoma
Mark Manzano, Thomas Günther, H. L. Ju, John Nicholas, Elizabeth T. Bartom, Adam Grundhoff, Eva Gottwein
Abstract
Kaposi's sarcoma-associated herpesvirus (KSHV) causes the aggressive disease primary effusion lymphoma (PEL). Here, we show that a viral transcription factor (vIRF3) cooperates with the cellular transcription factor IRF4 to control an oncogenic gene expression program in PEL cells. These proteins promote KSHV-mediated B cell transformation by activating the expression of prosurvival genes through super-enhancers. Our report thus demonstrates that this DNA tumor virus encodes a transcription factor that functions with cellular IRF4 to drive oncogenic transcriptional reprogramming.
Topics & Concepts
Primary effusion lymphomaKaposi's sarcoma-associated herpesvirusEnhancerBiologyTranscription factorReprogrammingIRF4GeneCancer researchVirologyGene expressionLymphomaInterferon regulatory factorsVirusGeneticsImmunologyHerpesviridaeViral diseaseViral-associated cancers and disordersLymphoma Diagnosis and TreatmentImmune Cell Function and Interaction