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Unstable EBV latency drives inflammation in multiple sclerosis patient derived spontaneous B cells
Epidemiological studies have demonstrated that Epstein-Barr virus (EBV) is a known etiologic risk factor, and perhaps prerequisite, for the development of MS. EBV establishes life-long latent infection in a subpopulation of memory B cells. Although the role of memory B cells in the pathobiology of M...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Journal Experts
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9915775/ https://www.ncbi.nlm.nih.gov/pubmed/36778367 http://dx.doi.org/10.21203/rs.3.rs-2398872/v1 |
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author | Soldan, Samantha Su, Chenhe Monaco, Maria Chiara Brown, Natalie Clauze, Annaliese Andrada, Frances Feder, Andries Planet, Paul Kossenkov, Andrew Schäffer, Daniel Ohayon, Joan Auslander, Noam Jacobson, Steve Lieberman, Paul |
author_facet | Soldan, Samantha Su, Chenhe Monaco, Maria Chiara Brown, Natalie Clauze, Annaliese Andrada, Frances Feder, Andries Planet, Paul Kossenkov, Andrew Schäffer, Daniel Ohayon, Joan Auslander, Noam Jacobson, Steve Lieberman, Paul |
author_sort | Soldan, Samantha |
collection | PubMed |
description | Epidemiological studies have demonstrated that Epstein-Barr virus (EBV) is a known etiologic risk factor, and perhaps prerequisite, for the development of MS. EBV establishes life-long latent infection in a subpopulation of memory B cells. Although the role of memory B cells in the pathobiology of MS is well established, studies characterizing EBV-associated mechanisms of B cell inflammation and disease pathogenesis in EBV (+) B cells from MS patients are limited. Accordingly, we analyzed spontaneous lymphoblastoid cell lines (SLCLs) from multiple sclerosis patients and healthy controls to study host-virus interactions in B cells, in the context of an individual’s endogenous EBV. We identify differences in EBV gene expression and regulation of both viral and cellular genes in SLCLs. Our data suggest that EBV latency is dysregulated in MS SLCLs with increased lytic gene expression observed in MS patient B cells, especially those generated from samples obtained during “active” disease. Moreover, we show increased inflammatory gene expression and cytokine production in MS patient SLCLs and demonstrate that tenofovir alafenamide, an antiviral that targets EBV replication, decreases EBV viral loads, EBV lytic gene expression, and EBV-mediated inflammation in both SLCLs and in a mixed lymphocyte assay. Collectively, these data suggest that dysregulation of EBV latency in MS drives a pro-inflammatory, pathogenic phenotype in memory B cells and that this response can be attenuated by suppressing EBV lytic activation. This study provides further support for the development of antiviral agents that target EBV-infection for use in MS. |
format | Online Article Text |
id | pubmed-9915775 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Journal Experts |
record_format | MEDLINE/PubMed |
spelling | pubmed-99157752023-02-11 Unstable EBV latency drives inflammation in multiple sclerosis patient derived spontaneous B cells Soldan, Samantha Su, Chenhe Monaco, Maria Chiara Brown, Natalie Clauze, Annaliese Andrada, Frances Feder, Andries Planet, Paul Kossenkov, Andrew Schäffer, Daniel Ohayon, Joan Auslander, Noam Jacobson, Steve Lieberman, Paul Res Sq Article Epidemiological studies have demonstrated that Epstein-Barr virus (EBV) is a known etiologic risk factor, and perhaps prerequisite, for the development of MS. EBV establishes life-long latent infection in a subpopulation of memory B cells. Although the role of memory B cells in the pathobiology of MS is well established, studies characterizing EBV-associated mechanisms of B cell inflammation and disease pathogenesis in EBV (+) B cells from MS patients are limited. Accordingly, we analyzed spontaneous lymphoblastoid cell lines (SLCLs) from multiple sclerosis patients and healthy controls to study host-virus interactions in B cells, in the context of an individual’s endogenous EBV. We identify differences in EBV gene expression and regulation of both viral and cellular genes in SLCLs. Our data suggest that EBV latency is dysregulated in MS SLCLs with increased lytic gene expression observed in MS patient B cells, especially those generated from samples obtained during “active” disease. Moreover, we show increased inflammatory gene expression and cytokine production in MS patient SLCLs and demonstrate that tenofovir alafenamide, an antiviral that targets EBV replication, decreases EBV viral loads, EBV lytic gene expression, and EBV-mediated inflammation in both SLCLs and in a mixed lymphocyte assay. Collectively, these data suggest that dysregulation of EBV latency in MS drives a pro-inflammatory, pathogenic phenotype in memory B cells and that this response can be attenuated by suppressing EBV lytic activation. This study provides further support for the development of antiviral agents that target EBV-infection for use in MS. American Journal Experts 2023-02-01 /pmc/articles/PMC9915775/ /pubmed/36778367 http://dx.doi.org/10.21203/rs.3.rs-2398872/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. |
spellingShingle | Article Soldan, Samantha Su, Chenhe Monaco, Maria Chiara Brown, Natalie Clauze, Annaliese Andrada, Frances Feder, Andries Planet, Paul Kossenkov, Andrew Schäffer, Daniel Ohayon, Joan Auslander, Noam Jacobson, Steve Lieberman, Paul Unstable EBV latency drives inflammation in multiple sclerosis patient derived spontaneous B cells |
title | Unstable EBV latency drives inflammation in multiple sclerosis patient derived spontaneous B cells |
title_full | Unstable EBV latency drives inflammation in multiple sclerosis patient derived spontaneous B cells |
title_fullStr | Unstable EBV latency drives inflammation in multiple sclerosis patient derived spontaneous B cells |
title_full_unstemmed | Unstable EBV latency drives inflammation in multiple sclerosis patient derived spontaneous B cells |
title_short | Unstable EBV latency drives inflammation in multiple sclerosis patient derived spontaneous B cells |
title_sort | unstable ebv latency drives inflammation in multiple sclerosis patient derived spontaneous b cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9915775/ https://www.ncbi.nlm.nih.gov/pubmed/36778367 http://dx.doi.org/10.21203/rs.3.rs-2398872/v1 |
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