High-Throughput Sequence Analysis of Peripheral T-Cell Lymphomas Indicates Subtype-Specific Viral Gene Expression Patterns and Immune Cell Microenvironments

ABSTRACT Certain peripheral T-cell lymphomas (PTCLs) have been associated with viral infection, particularly infection with Epstein-Barr virus (EBV). However, a comprehensive virome analysis across PTCLs has not previously been reported. Here we utilized published whole-transcriptome RNA sequencing...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Hani Nakhoul, Zhen Lin, Xia Wang, Claire Roberts, Yan Dong, Erik Flemington
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	B-cell receptor diversity EBV Epstein-Barr virus Kaposi's sarcoma-associated herpesvirus T cell human T-cell leukemia virus Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/15e14c9d0ff04323b8dee81d6a8ce099
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:15e14c9d0ff04323b8dee81d6a8ce099
record_format	dspace
spelling	oai:doaj.org-article:15e14c9d0ff04323b8dee81d6a8ce0992021-11-15T15:22:27ZHigh-Throughput Sequence Analysis of Peripheral T-Cell Lymphomas Indicates Subtype-Specific Viral Gene Expression Patterns and Immune Cell Microenvironments10.1128/mSphere.00248-192379-5042https://doaj.org/article/15e14c9d0ff04323b8dee81d6a8ce0992019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00248-19https://doaj.org/toc/2379-5042ABSTRACT Certain peripheral T-cell lymphomas (PTCLs) have been associated with viral infection, particularly infection with Epstein-Barr virus (EBV). However, a comprehensive virome analysis across PTCLs has not previously been reported. Here we utilized published whole-transcriptome RNA sequencing (RNA-seq) data sets from seven different PTCL studies and new RNA-seq data from our laboratory to screen for virus association, to analyze viral gene expression, and to assess B- and T-cell receptor diversity paradigms across PTCL subtypes. In addition to identifying EBV in angioimmunoblastic T-cell lymphoma (AITL) and extranodal NK/T-cell lymphoma (ENKTL), two PTCL subtypes with well-established EBV associations, we also detected EBV in several cases of anaplastic large-cell lymphoma (ALCL), and we found evidence of infection by the oncogenic viruses Kaposi’s sarcoma-associated herpesvirus and human T-cell leukemia virus type 1 in isolated PTCL cases. In AITLs, EBV gene expression analysis showed expression of immediate early, early, and late lytic genes, suggesting either low-level lytic gene expression or productive infection in a subset of EBV-infected B-lymphocyte stromal cells. Deconvolution of immune cell subpopulations demonstrated a greater B-cell signal in AITLs than in other PTCL subtypes, consistent with a larger role for B-cell support in the pathogenesis of AITL. Reconstructed T-cell receptor (TCR) and B-cell receptor (BCR) repertoires demonstrated increased BCR diversity in AITLs, consistent with a possible EBV-driven polyclonal response. These findings indicate potential alternative roles for EBV in PTCLs, in addition to the canonical oncogenic mechanisms associated with EBV latent infection. Our findings also suggest the involvement of other viruses in PTCL pathogenesis and demonstrate immunological alterations associated with these cancers. IMPORTANCE In this study, we utilized next-generation sequencing data from 7 different studies of peripheral T-cell lymphoma (PTCL) patient samples to globally assess viral associations, provide insights into the contributions of EBV gene expression to the tumor phenotype, and assess the unique roles of EBV in modulating the immune cell tumor microenvironment. These studies revealed potential roles for EBV replication genes in some PTCL subtypes, the possible role of additional human tumor viruses in rare cases of PTCLs, and a role for EBV in providing a unique immune microenvironmental niche in one subtype of PTCLs. Together, these studies provide new insights into the understudied role of tumor viruses in PTCLs.Hani NakhoulZhen LinXia WangClaire RobertsYan DongErik FlemingtonAmerican Society for MicrobiologyarticleB-cell receptor diversityEBVEpstein-Barr virusKaposi's sarcoma-associated herpesvirusT cellhuman T-cell leukemia virusMicrobiologyQR1-502ENmSphere, Vol 4, Iss 4 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	B-cell receptor diversity EBV Epstein-Barr virus Kaposi's sarcoma-associated herpesvirus T cell human T-cell leukemia virus Microbiology QR1-502
spellingShingle	B-cell receptor diversity EBV Epstein-Barr virus Kaposi's sarcoma-associated herpesvirus T cell human T-cell leukemia virus Microbiology QR1-502 Hani Nakhoul Zhen Lin Xia Wang Claire Roberts Yan Dong Erik Flemington High-Throughput Sequence Analysis of Peripheral T-Cell Lymphomas Indicates Subtype-Specific Viral Gene Expression Patterns and Immune Cell Microenvironments
description	ABSTRACT Certain peripheral T-cell lymphomas (PTCLs) have been associated with viral infection, particularly infection with Epstein-Barr virus (EBV). However, a comprehensive virome analysis across PTCLs has not previously been reported. Here we utilized published whole-transcriptome RNA sequencing (RNA-seq) data sets from seven different PTCL studies and new RNA-seq data from our laboratory to screen for virus association, to analyze viral gene expression, and to assess B- and T-cell receptor diversity paradigms across PTCL subtypes. In addition to identifying EBV in angioimmunoblastic T-cell lymphoma (AITL) and extranodal NK/T-cell lymphoma (ENKTL), two PTCL subtypes with well-established EBV associations, we also detected EBV in several cases of anaplastic large-cell lymphoma (ALCL), and we found evidence of infection by the oncogenic viruses Kaposi’s sarcoma-associated herpesvirus and human T-cell leukemia virus type 1 in isolated PTCL cases. In AITLs, EBV gene expression analysis showed expression of immediate early, early, and late lytic genes, suggesting either low-level lytic gene expression or productive infection in a subset of EBV-infected B-lymphocyte stromal cells. Deconvolution of immune cell subpopulations demonstrated a greater B-cell signal in AITLs than in other PTCL subtypes, consistent with a larger role for B-cell support in the pathogenesis of AITL. Reconstructed T-cell receptor (TCR) and B-cell receptor (BCR) repertoires demonstrated increased BCR diversity in AITLs, consistent with a possible EBV-driven polyclonal response. These findings indicate potential alternative roles for EBV in PTCLs, in addition to the canonical oncogenic mechanisms associated with EBV latent infection. Our findings also suggest the involvement of other viruses in PTCL pathogenesis and demonstrate immunological alterations associated with these cancers. IMPORTANCE In this study, we utilized next-generation sequencing data from 7 different studies of peripheral T-cell lymphoma (PTCL) patient samples to globally assess viral associations, provide insights into the contributions of EBV gene expression to the tumor phenotype, and assess the unique roles of EBV in modulating the immune cell tumor microenvironment. These studies revealed potential roles for EBV replication genes in some PTCL subtypes, the possible role of additional human tumor viruses in rare cases of PTCLs, and a role for EBV in providing a unique immune microenvironmental niche in one subtype of PTCLs. Together, these studies provide new insights into the understudied role of tumor viruses in PTCLs.
format	article
author	Hani Nakhoul Zhen Lin Xia Wang Claire Roberts Yan Dong Erik Flemington
author_facet	Hani Nakhoul Zhen Lin Xia Wang Claire Roberts Yan Dong Erik Flemington
author_sort	Hani Nakhoul
title	High-Throughput Sequence Analysis of Peripheral T-Cell Lymphomas Indicates Subtype-Specific Viral Gene Expression Patterns and Immune Cell Microenvironments
title_short	High-Throughput Sequence Analysis of Peripheral T-Cell Lymphomas Indicates Subtype-Specific Viral Gene Expression Patterns and Immune Cell Microenvironments
title_full	High-Throughput Sequence Analysis of Peripheral T-Cell Lymphomas Indicates Subtype-Specific Viral Gene Expression Patterns and Immune Cell Microenvironments
title_fullStr	High-Throughput Sequence Analysis of Peripheral T-Cell Lymphomas Indicates Subtype-Specific Viral Gene Expression Patterns and Immune Cell Microenvironments
title_full_unstemmed	High-Throughput Sequence Analysis of Peripheral T-Cell Lymphomas Indicates Subtype-Specific Viral Gene Expression Patterns and Immune Cell Microenvironments
title_sort	high-throughput sequence analysis of peripheral t-cell lymphomas indicates subtype-specific viral gene expression patterns and immune cell microenvironments
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/15e14c9d0ff04323b8dee81d6a8ce099
work_keys_str_mv	AT haninakhoul highthroughputsequenceanalysisofperipheraltcelllymphomasindicatessubtypespecificviralgeneexpressionpatternsandimmunecellmicroenvironments AT zhenlin highthroughputsequenceanalysisofperipheraltcelllymphomasindicatessubtypespecificviralgeneexpressionpatternsandimmunecellmicroenvironments AT xiawang highthroughputsequenceanalysisofperipheraltcelllymphomasindicatessubtypespecificviralgeneexpressionpatternsandimmunecellmicroenvironments AT claireroberts highthroughputsequenceanalysisofperipheraltcelllymphomasindicatessubtypespecificviralgeneexpressionpatternsandimmunecellmicroenvironments AT yandong highthroughputsequenceanalysisofperipheraltcelllymphomasindicatessubtypespecificviralgeneexpressionpatternsandimmunecellmicroenvironments AT erikflemington highthroughputsequenceanalysisofperipheraltcelllymphomasindicatessubtypespecificviralgeneexpressionpatternsandimmunecellmicroenvironments
_version_	1718427993282445312

High-Throughput Sequence Analysis of Peripheral T-Cell Lymphomas Indicates Subtype-Specific Viral Gene Expression Patterns and Immune Cell Microenvironments

Ejemplares similares