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A Gammaherpesvirus MicroRNA Targets EWSR1 (Ewing Sarcoma Breakpoint Region 1) In Vivo To Promote Latent Infection of Germinal Center B Cells
Gammaherpesviruses, including the human pathogens Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV), directly contribute to the genesis of multiple types of malignancies, including B cell lymphomas. In vivo, these viruses infect B cells and manipulate B cell biology to esta...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667617/ https://www.ncbi.nlm.nih.gov/pubmed/31363027 http://dx.doi.org/10.1128/mBio.00996-19 |
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author | Wang, Yiping Feldman, Emily R. Bullard, Whitney L. Tibbetts, Scott A. |
author_facet | Wang, Yiping Feldman, Emily R. Bullard, Whitney L. Tibbetts, Scott A. |
author_sort | Wang, Yiping |
collection | PubMed |
description | Gammaherpesviruses, including the human pathogens Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV), directly contribute to the genesis of multiple types of malignancies, including B cell lymphomas. In vivo, these viruses infect B cells and manipulate B cell biology to establish lifelong latent infection. To accomplish this, gammaherpesviruses employ an array of gene products, including microRNAs (miRNAs). Although numerous host mRNA targets of gammaherpesvirus miRNAs have been identified, the in vivo relevance of repression of these targets remains elusive due to species restriction. Murine gammaherpesvirus 68 (MHV68) provides a robust virus-host system to dissect the in vivo function of conserved gammaherpesvirus genetic elements. We identified here MHV68 mghv-miR-M1-7-5p as critical for in vivo infection and then validated host EWSR1 (Ewing sarcoma breakpoint region 1) as the predominant target for this miRNA. Using novel, target-specific shRNA-expressing viruses, we determined that EWSR1 repression in vivo was essential for germinal center B cell infection. These findings provide the first in vivo demonstration of the biological significance of repression of a specific host mRNA by a gammaherpesvirus miRNA. |
format | Online Article Text |
id | pubmed-6667617 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-66676172019-08-06 A Gammaherpesvirus MicroRNA Targets EWSR1 (Ewing Sarcoma Breakpoint Region 1) In Vivo To Promote Latent Infection of Germinal Center B Cells Wang, Yiping Feldman, Emily R. Bullard, Whitney L. Tibbetts, Scott A. mBio Research Article Gammaherpesviruses, including the human pathogens Epstein-Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV), directly contribute to the genesis of multiple types of malignancies, including B cell lymphomas. In vivo, these viruses infect B cells and manipulate B cell biology to establish lifelong latent infection. To accomplish this, gammaherpesviruses employ an array of gene products, including microRNAs (miRNAs). Although numerous host mRNA targets of gammaherpesvirus miRNAs have been identified, the in vivo relevance of repression of these targets remains elusive due to species restriction. Murine gammaherpesvirus 68 (MHV68) provides a robust virus-host system to dissect the in vivo function of conserved gammaherpesvirus genetic elements. We identified here MHV68 mghv-miR-M1-7-5p as critical for in vivo infection and then validated host EWSR1 (Ewing sarcoma breakpoint region 1) as the predominant target for this miRNA. Using novel, target-specific shRNA-expressing viruses, we determined that EWSR1 repression in vivo was essential for germinal center B cell infection. These findings provide the first in vivo demonstration of the biological significance of repression of a specific host mRNA by a gammaherpesvirus miRNA. American Society for Microbiology 2019-07-30 /pmc/articles/PMC6667617/ /pubmed/31363027 http://dx.doi.org/10.1128/mBio.00996-19 Text en Copyright © 2019 Wang et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Wang, Yiping Feldman, Emily R. Bullard, Whitney L. Tibbetts, Scott A. A Gammaherpesvirus MicroRNA Targets EWSR1 (Ewing Sarcoma Breakpoint Region 1) In Vivo To Promote Latent Infection of Germinal Center B Cells |
title | A Gammaherpesvirus MicroRNA Targets EWSR1 (Ewing Sarcoma Breakpoint Region 1) In Vivo To Promote Latent Infection of Germinal Center B Cells |
title_full | A Gammaherpesvirus MicroRNA Targets EWSR1 (Ewing Sarcoma Breakpoint Region 1) In Vivo To Promote Latent Infection of Germinal Center B Cells |
title_fullStr | A Gammaherpesvirus MicroRNA Targets EWSR1 (Ewing Sarcoma Breakpoint Region 1) In Vivo To Promote Latent Infection of Germinal Center B Cells |
title_full_unstemmed | A Gammaherpesvirus MicroRNA Targets EWSR1 (Ewing Sarcoma Breakpoint Region 1) In Vivo To Promote Latent Infection of Germinal Center B Cells |
title_short | A Gammaherpesvirus MicroRNA Targets EWSR1 (Ewing Sarcoma Breakpoint Region 1) In Vivo To Promote Latent Infection of Germinal Center B Cells |
title_sort | gammaherpesvirus microrna targets ewsr1 (ewing sarcoma breakpoint region 1) in vivo to promote latent infection of germinal center b cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667617/ https://www.ncbi.nlm.nih.gov/pubmed/31363027 http://dx.doi.org/10.1128/mBio.00996-19 |
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