Epstein-Barr virus evades restrictive host chromatin closure by subverting B cell activation and germinal center regulatory loci
Summary: 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 sen...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-08-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723009695 |
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| author | Elliott D. SoRelle Nicolás M. Reinoso-Vizcaino Joanne Dai Ashley P. Barry Cliburn Chan Micah A. Luftig |
| author_facet | Elliott D. SoRelle Nicolás M. Reinoso-Vizcaino Joanne Dai Ashley P. Barry Cliburn Chan Micah A. Luftig |
| author_sort | Elliott D. SoRelle |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-03-12T11:53:10Z |
| format | Article |
| id | doaj.art-113e187d3bce4a3f8eb3aeaef58addb1 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-12T11:53:10Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-113e187d3bce4a3f8eb3aeaef58addb12023-08-31T05:02:19ZengElsevierCell Reports2211-12472023-08-01428112958Epstein-Barr virus evades restrictive host chromatin closure by subverting B cell activation and germinal center regulatory lociElliott D. SoRelle0Nicolás M. Reinoso-Vizcaino1Joanne Dai2Ashley P. Barry3Cliburn Chan4Micah A. Luftig5Department of Molecular Genetics and Microbiology, Duke Center for Virology, Duke University School of Medicine, Durham, NC 27710, USA; Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC 27710, USA; Corresponding authorDepartment of Molecular Genetics and Microbiology, Duke Center for Virology, Duke University School of Medicine, Durham, NC 27710, USADepartment of Molecular Genetics and Microbiology, Duke Center for Virology, Duke University School of Medicine, Durham, NC 27710, USADepartment of Molecular Genetics and Microbiology, Duke Center for Virology, Duke University School of Medicine, Durham, NC 27710, USADepartment of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC 27710, USADepartment of Molecular Genetics and Microbiology, Duke Center for Virology, Duke University School of Medicine, Durham, NC 27710, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124723009695CP: ImmunologyCP: Microbiology |
| spellingShingle | Elliott D. SoRelle Nicolás M. Reinoso-Vizcaino Joanne Dai Ashley P. Barry Cliburn Chan Micah A. Luftig Epstein-Barr virus evades restrictive host chromatin closure by subverting B cell activation and germinal center regulatory loci Cell Reports CP: Immunology CP: Microbiology |
| title | Epstein-Barr virus evades restrictive host chromatin closure by subverting B cell activation and germinal center regulatory loci |
| title_full | Epstein-Barr virus evades restrictive host chromatin closure by subverting B cell activation and germinal center regulatory loci |
| title_fullStr | Epstein-Barr virus evades restrictive host chromatin closure by subverting B cell activation and germinal center regulatory loci |
| title_full_unstemmed | Epstein-Barr virus evades restrictive host chromatin closure by subverting B cell activation and germinal center regulatory loci |
| title_short | Epstein-Barr virus evades restrictive host chromatin closure by subverting B cell activation and germinal center regulatory loci |
| title_sort | epstein barr virus evades restrictive host chromatin closure by subverting b cell activation and germinal center regulatory loci |
| topic | CP: Immunology CP: Microbiology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723009695 |
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