Epstein-Barr Virus Induces Adhesion Receptor CD226 (DNAM-1) Expression during Primary B-Cell Transformation into Lymphoblastoid Cell Lines

ABSTRACT Epstein-Barr virus (EBV), an oncogenic herpesvirus, infects and transforms primary B cells into immortal lymphoblastoid cell lines (LCLs), providing a model for EBV-mediated tumorigenesis. EBV transformation stimulates robust homotypic aggregation, indicating that EBV induces molecules that...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Lisa Grossman, Chris Chang, Joanne Dai, Pavel A. Nikitin, Dereje D. Jima, Sandeep S. Dave, Micah A. Luftig
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	CD226 DNAM-1 Epstein-Barr virus LMP1 NF-κB adhesion molecules Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/8781b480d55c41a78647de24435d873a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8781b480d55c41a78647de24435d873a
record_format	dspace
spelling	oai:doaj.org-article:8781b480d55c41a78647de24435d873a2021-11-15T15:21:51ZEpstein-Barr Virus Induces Adhesion Receptor CD226 (DNAM-1) Expression during Primary B-Cell Transformation into Lymphoblastoid Cell Lines10.1128/mSphere.00305-172379-5042https://doaj.org/article/8781b480d55c41a78647de24435d873a2017-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00305-17https://doaj.org/toc/2379-5042ABSTRACT Epstein-Barr virus (EBV), an oncogenic herpesvirus, infects and transforms primary B cells into immortal lymphoblastoid cell lines (LCLs), providing a model for EBV-mediated tumorigenesis. EBV transformation stimulates robust homotypic aggregation, indicating that EBV induces molecules that mediate cell-cell adhesion. We report that EBV potently induced expression of the adhesion molecule CD226, which is not normally expressed on B cells. We found that early after infection of primary B cells, EBV promoted an increase in CD226 mRNA and protein expression. CD226 levels increased further from early proliferating EBV-positive B cells to LCLs. We found that CD226 expression on B cells was independent of B-cell activation as CpG DNA failed to induce CD226 to the extent of EBV infection. CD226 expression was high in EBV-infected B cells expressing the latency III growth program, but low in EBV-negative and EBV latency I-infected B-lymphoma cell lines. We validated this correlation by demonstrating that the latency III characteristic EBV NF-κB activator, latent membrane protein 1 (LMP1), was sufficient for CD226 upregulation and that CD226 was more highly expressed in lymphomas with increased NF-κB activity. Finally, we found that CD226 was not important for LCL steady-state growth, survival in response to apoptotic stress, homotypic aggregation, or adhesion to activated endothelial cells. These findings collectively suggest that EBV induces expression of a cell adhesion molecule on primary B cells that may play a role in the tumor microenvironment of EBV-associated B-cell malignancies or facilitate adhesion in the establishment of latency in vivo. IMPORTANCE Epstein-Barr virus (EBV) is a common human herpesvirus that establishes latency in B cells. While EBV infection is asymptomatic for most individuals, immune-suppressed individuals are at significantly higher risk of a form of EBV latent infection in which infected B cells are reactivated, grow unchecked, and generate lymphomas. This form of latency is modeled in the laboratory by infecting B cells from the blood of normal human donors in vitro. In this model, we identified a protein called CD226 that is induced by EBV but is not normally expressed on B cells. Rather, it is known to play a role in aggregation and survival signaling of non-B cells in the immune system. Cultures of EBV-infected cells adhere to one another in “clumps,” and while the proteins that are responsible for this cellular aggregation are not fully understood, we hypothesized that this form of cellular aggregation may provide a survival advantage. In this article, we characterize the mechanism by which EBV induces this protein and its expression on lymphoma tissue and cell lines and characterize EBV-infected cell lines in which CD226 has been knocked out.Lisa GrossmanChris ChangJoanne DaiPavel A. NikitinDereje D. JimaSandeep S. DaveMicah A. LuftigAmerican Society for MicrobiologyarticleCD226DNAM-1Epstein-Barr virusLMP1NF-κBadhesion moleculesMicrobiologyQR1-502ENmSphere, Vol 2, Iss 6 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	CD226 DNAM-1 Epstein-Barr virus LMP1 NF-κB adhesion molecules Microbiology QR1-502
spellingShingle	CD226 DNAM-1 Epstein-Barr virus LMP1 NF-κB adhesion molecules Microbiology QR1-502 Lisa Grossman Chris Chang Joanne Dai Pavel A. Nikitin Dereje D. Jima Sandeep S. Dave Micah A. Luftig Epstein-Barr Virus Induces Adhesion Receptor CD226 (DNAM-1) Expression during Primary B-Cell Transformation into Lymphoblastoid Cell Lines
description	ABSTRACT Epstein-Barr virus (EBV), an oncogenic herpesvirus, infects and transforms primary B cells into immortal lymphoblastoid cell lines (LCLs), providing a model for EBV-mediated tumorigenesis. EBV transformation stimulates robust homotypic aggregation, indicating that EBV induces molecules that mediate cell-cell adhesion. We report that EBV potently induced expression of the adhesion molecule CD226, which is not normally expressed on B cells. We found that early after infection of primary B cells, EBV promoted an increase in CD226 mRNA and protein expression. CD226 levels increased further from early proliferating EBV-positive B cells to LCLs. We found that CD226 expression on B cells was independent of B-cell activation as CpG DNA failed to induce CD226 to the extent of EBV infection. CD226 expression was high in EBV-infected B cells expressing the latency III growth program, but low in EBV-negative and EBV latency I-infected B-lymphoma cell lines. We validated this correlation by demonstrating that the latency III characteristic EBV NF-κB activator, latent membrane protein 1 (LMP1), was sufficient for CD226 upregulation and that CD226 was more highly expressed in lymphomas with increased NF-κB activity. Finally, we found that CD226 was not important for LCL steady-state growth, survival in response to apoptotic stress, homotypic aggregation, or adhesion to activated endothelial cells. These findings collectively suggest that EBV induces expression of a cell adhesion molecule on primary B cells that may play a role in the tumor microenvironment of EBV-associated B-cell malignancies or facilitate adhesion in the establishment of latency in vivo. IMPORTANCE Epstein-Barr virus (EBV) is a common human herpesvirus that establishes latency in B cells. While EBV infection is asymptomatic for most individuals, immune-suppressed individuals are at significantly higher risk of a form of EBV latent infection in which infected B cells are reactivated, grow unchecked, and generate lymphomas. This form of latency is modeled in the laboratory by infecting B cells from the blood of normal human donors in vitro. In this model, we identified a protein called CD226 that is induced by EBV but is not normally expressed on B cells. Rather, it is known to play a role in aggregation and survival signaling of non-B cells in the immune system. Cultures of EBV-infected cells adhere to one another in “clumps,” and while the proteins that are responsible for this cellular aggregation are not fully understood, we hypothesized that this form of cellular aggregation may provide a survival advantage. In this article, we characterize the mechanism by which EBV induces this protein and its expression on lymphoma tissue and cell lines and characterize EBV-infected cell lines in which CD226 has been knocked out.
format	article
author	Lisa Grossman Chris Chang Joanne Dai Pavel A. Nikitin Dereje D. Jima Sandeep S. Dave Micah A. Luftig
author_facet	Lisa Grossman Chris Chang Joanne Dai Pavel A. Nikitin Dereje D. Jima Sandeep S. Dave Micah A. Luftig
author_sort	Lisa Grossman
title	Epstein-Barr Virus Induces Adhesion Receptor CD226 (DNAM-1) Expression during Primary B-Cell Transformation into Lymphoblastoid Cell Lines
title_short	Epstein-Barr Virus Induces Adhesion Receptor CD226 (DNAM-1) Expression during Primary B-Cell Transformation into Lymphoblastoid Cell Lines
title_full	Epstein-Barr Virus Induces Adhesion Receptor CD226 (DNAM-1) Expression during Primary B-Cell Transformation into Lymphoblastoid Cell Lines
title_fullStr	Epstein-Barr Virus Induces Adhesion Receptor CD226 (DNAM-1) Expression during Primary B-Cell Transformation into Lymphoblastoid Cell Lines
title_full_unstemmed	Epstein-Barr Virus Induces Adhesion Receptor CD226 (DNAM-1) Expression during Primary B-Cell Transformation into Lymphoblastoid Cell Lines
title_sort	epstein-barr virus induces adhesion receptor cd226 (dnam-1) expression during primary b-cell transformation into lymphoblastoid cell lines
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/8781b480d55c41a78647de24435d873a
work_keys_str_mv	AT lisagrossman epsteinbarrvirusinducesadhesionreceptorcd226dnam1expressionduringprimarybcelltransformationintolymphoblastoidcelllines AT chrischang epsteinbarrvirusinducesadhesionreceptorcd226dnam1expressionduringprimarybcelltransformationintolymphoblastoidcelllines AT joannedai epsteinbarrvirusinducesadhesionreceptorcd226dnam1expressionduringprimarybcelltransformationintolymphoblastoidcelllines AT pavelanikitin epsteinbarrvirusinducesadhesionreceptorcd226dnam1expressionduringprimarybcelltransformationintolymphoblastoidcelllines AT derejedjima epsteinbarrvirusinducesadhesionreceptorcd226dnam1expressionduringprimarybcelltransformationintolymphoblastoidcelllines AT sandeepsdave epsteinbarrvirusinducesadhesionreceptorcd226dnam1expressionduringprimarybcelltransformationintolymphoblastoidcelllines AT micahaluftig epsteinbarrvirusinducesadhesionreceptorcd226dnam1expressionduringprimarybcelltransformationintolymphoblastoidcelllines
_version_	1718428081719345152

Epstein-Barr Virus Induces Adhesion Receptor CD226 (DNAM-1) Expression during Primary B-Cell Transformation into Lymphoblastoid Cell Lines

Ejemplares similares