染色质可及性在基因表达和生物反应程序中起着根本作用，且可以被病原体操控。本研究捕获了EB病毒感染过程中个体B细胞的动态染色质景观。通过抗病毒感应引发的停滞和增殖相关的DNA损伤，导致EBV阳性细胞经历了全局可及性的减少。增殖中的EBV阳性细胞发展了与体内生发中心表型相似的表达相关结构和结合位可及性谱。令人惊讶的是，尽管BCL6表达下调，EBV依然诱导了暗带、明带和后生发中心B细胞的染色质特征。单细胞转座子可及性染色质测序（scATAC-seq）、单细胞RNA测序（scRNA-seq）和染色质免疫沉淀测序（ChIP-seq）数据的整合，可以进行基因组范围的顺式调控预测，揭示了EB病毒核抗原在表型特异性调控生发中心B细胞的激活、存活和免疫逃逸中的作用。基于生物信息学鉴定的调控因子（MEF2C和NFE2L2）的敲除验证了对EBV感染引起的生发中心表型及EBNA相关位点的基因表达调控（CD274/PD-L1）。这些数据和方法可用于高分辨率地研究EBV与宿主相互作用、B细胞命运和病毒介导的淋巴瘤发生机制。版权所有 © 2023 作者或授权人。由Elsevier Inc.出版，版权所有。

Chromatin accessibility fundamentally governs gene expression and biological response programs that can be manipulated by pathogens. Here we capture dynamic chromatin landscapes of individual B cells during Epstein-Barr virus (EBV) infection. EBV+ cells that exhibit arrest via antiviral sensing and proliferation-linked DNA damage experience global accessibility reduction. Proliferative EBV+ cells develop expression-linked architectures and motif accessibility profiles resembling in vivo germinal center (GC) phenotypes. Remarkably, EBV elicits dark zone (DZ), light zone (LZ), and post-GC B cell chromatin features despite BCL6 downregulation. Integration of single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq), single-cell RNA sequencing (scRNA-seq), and chromatin immunoprecipitation sequencing (ChIP-seq) data enables genome-wide cis-regulatory predictions implicating EBV nuclear antigens (EBNAs) in phenotype-specific control of GC B cell activation, survival, and immune evasion. Knockouts validate bioinformatically identified regulators (MEF2C and NFE2L2) of EBV-induced GC phenotypes and EBNA-associated loci that regulate gene expression (CD274/PD-L1). These data and methods can inform high-resolution investigations of EBV-host interactions, B cell fates, and virus-mediated lymphomagenesis.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.