A Gammaherpesvirus MicroRNA Targets EWSR1 (Ewing Sarcoma Breakpoint Region 1) <italic toggle="yes">In Vivo</italic> To Promote Latent Infection of Germinal Center B Cells

ABSTRACT 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 biolog...

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Autores principales:	Yiping Wang, Emily R. Feldman, Whitney L. Bullard, Scott A. Tibbetts
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	EWSR1 MHV68 gammaherpesvirus in vivo miRNA Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e74abf7a3e0c4025a165313007ce93b7
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spelling	oai:doaj.org-article:e74abf7a3e0c4025a165313007ce93b72021-11-15T16:22:10ZA Gammaherpesvirus MicroRNA Targets EWSR1 (Ewing Sarcoma Breakpoint Region 1) <italic toggle="yes">In Vivo</italic> To Promote Latent Infection of Germinal Center B Cells10.1128/mBio.00996-192150-7511https://doaj.org/article/e74abf7a3e0c4025a165313007ce93b72019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00996-19https://doaj.org/toc/2150-7511ABSTRACT 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. IMPORTANCE 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. In vivo, these viruses infect B cells and manipulate B cell biology to establish lifelong infection. To accomplish this, gammaherpesviruses employ an array of gene products, including miRNAs, short noncoding RNAs that bind to and repress protein synthesis from specific target mRNAs. The in vivo relevance of repression of targets of gammaherpesvirus miRNAs remains highly elusive. Here, we identified a murine gammaherpesvirus miRNA as critical for in vivo infection and validated the host mRNA EWSR1 (Ewing sarcoma breakpoint region 1) as the predominant target for this miRNA. Using a novel technology, we demonstrated that repression of EWSR1 was essential for in vivo infection of the critical B cell reservoir. These findings provide the first in vivo demonstration of the significance of repression of a specific host mRNA by a gammaherpesvirus miRNA.Yiping WangEmily R. FeldmanWhitney L. BullardScott A. TibbettsAmerican Society for MicrobiologyarticleEWSR1MHV68gammaherpesvirusin vivomiRNAMicrobiologyQR1-502ENmBio, Vol 10, Iss 4 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	EWSR1 MHV68 gammaherpesvirus in vivo miRNA Microbiology QR1-502
spellingShingle	EWSR1 MHV68 gammaherpesvirus in vivo miRNA Microbiology QR1-502 Yiping Wang Emily R. Feldman Whitney L. Bullard Scott A. Tibbetts A Gammaherpesvirus MicroRNA Targets EWSR1 (Ewing Sarcoma Breakpoint Region 1) <italic toggle="yes">In Vivo</italic> To Promote Latent Infection of Germinal Center B Cells
description	ABSTRACT 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. IMPORTANCE 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. In vivo, these viruses infect B cells and manipulate B cell biology to establish lifelong infection. To accomplish this, gammaherpesviruses employ an array of gene products, including miRNAs, short noncoding RNAs that bind to and repress protein synthesis from specific target mRNAs. The in vivo relevance of repression of targets of gammaherpesvirus miRNAs remains highly elusive. Here, we identified a murine gammaherpesvirus miRNA as critical for in vivo infection and validated the host mRNA EWSR1 (Ewing sarcoma breakpoint region 1) as the predominant target for this miRNA. Using a novel technology, we demonstrated that repression of EWSR1 was essential for in vivo infection of the critical B cell reservoir. These findings provide the first in vivo demonstration of the significance of repression of a specific host mRNA by a gammaherpesvirus miRNA.
format	article
author	Yiping Wang Emily R. Feldman Whitney L. Bullard Scott A. Tibbetts
author_facet	Yiping Wang Emily R. Feldman Whitney L. Bullard Scott A. Tibbetts
author_sort	Yiping Wang
title	A Gammaherpesvirus MicroRNA Targets EWSR1 (Ewing Sarcoma Breakpoint Region 1) <italic toggle="yes">In Vivo</italic> To Promote Latent Infection of Germinal Center B Cells
title_short	A Gammaherpesvirus MicroRNA Targets EWSR1 (Ewing Sarcoma Breakpoint Region 1) <italic toggle="yes">In Vivo</italic> To Promote Latent Infection of Germinal Center B Cells
title_full	A Gammaherpesvirus MicroRNA Targets EWSR1 (Ewing Sarcoma Breakpoint Region 1) <italic toggle="yes">In Vivo</italic> To Promote Latent Infection of Germinal Center B Cells
title_fullStr	A Gammaherpesvirus MicroRNA Targets EWSR1 (Ewing Sarcoma Breakpoint Region 1) <italic toggle="yes">In Vivo</italic> To Promote Latent Infection of Germinal Center B Cells
title_full_unstemmed	A Gammaherpesvirus MicroRNA Targets EWSR1 (Ewing Sarcoma Breakpoint Region 1) <italic toggle="yes">In Vivo</italic> To Promote Latent Infection of Germinal Center B Cells
title_sort	gammaherpesvirus microrna targets ewsr1 (ewing sarcoma breakpoint region 1) <italic toggle="yes">in vivo</italic> to promote latent infection of germinal center b cells
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/e74abf7a3e0c4025a165313007ce93b7
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A Gammaherpesvirus MicroRNA Targets EWSR1 (Ewing Sarcoma Breakpoint Region 1) <italic toggle="yes">In Vivo</italic> To Promote Latent Infection of Germinal Center B Cells

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