Publications [#383712] of Chi Wei C. Chan

Papers Published

1. SoRelle, ED; Reinoso-Vizcaino, NM; Dai, J; Barry, AP; Chan, C; Luftig, MA, Epstein-Barr virus evades restrictive host chromatin closure by subverting B cell activation and germinal center regulatory loci., Cell Rep, vol. 42 no. 8 (August, 2023), pp. 112958 [doi]
   (last updated on 2026/01/17)

   Abstract:
   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.