Imaging Mass Spectrometry and Proteome Analysis of Marek’s Disease Virus-Induced Tumors

ABSTRACT The highly oncogenic alphaherpesvirus Marek’s disease virus (MDV) causes immense economic losses in the poultry industry. MDV induces a variety of symptoms in infected chickens, including neurological disorders and immunosuppression. Most notably, MDV induces transformation of lymphocytes,...

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Autores principales:	V. I. Pauker, L. D. Bertzbach, A. Hohmann, A. Kheimar, J. P. Teifke, T. C. Mettenleiter, A. Karger, B. B. Kaufer
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Marek’s disease virus imaging mass spectrometry lymphoma noncontact laser capture microdissection proteome tumor Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/958a24e0223c45028030cb36f8139b84
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spelling	oai:doaj.org-article:958a24e0223c45028030cb36f8139b842021-11-15T15:22:04ZImaging Mass Spectrometry and Proteome Analysis of Marek’s Disease Virus-Induced Tumors10.1128/mSphere.00569-182379-5042https://doaj.org/article/958a24e0223c45028030cb36f8139b842019-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00569-18https://doaj.org/toc/2379-5042ABSTRACT The highly oncogenic alphaherpesvirus Marek’s disease virus (MDV) causes immense economic losses in the poultry industry. MDV induces a variety of symptoms in infected chickens, including neurological disorders and immunosuppression. Most notably, MDV induces transformation of lymphocytes, leading to T cell lymphomas in visceral organs with a mortality of up to 100%. While several factors involved in MDV tumorigenesis have been identified, the transformation process and tumor composition remain poorly understood. Here we developed an imaging mass spectrometry (IMS) approach that allows sensitive visualization of MDV-induced lymphoma with a specific mass profile and precise differentiation from the surrounding tissue. To identify potential tumor markers in tumors derived from a very virulent wild-type virus and a telomerase RNA-deficient mutant, we performed laser capture microdissection (LCM) and thereby obtained tumor samples with no or minimal contamination from surrounding nontumor tissue. The proteomes of the LCM samples were subsequently analyzed by quantitative mass spectrometry based on stable isotope labeling. Several proteins, like interferon gamma-inducible protein 30 and a 70-kDa heat shock protein, were identified that are differentially expressed in tumor tissue compared to surrounding tissue and naive T cells. Taken together, our results demonstrate for the first time that MDV-induced tumors can be visualized using IMS, and we identified potential MDV tumor markers by analyzing the proteomes of virus-induced tumors. IMPORTANCE Marek’s disease virus (MDV) is an oncogenic alphaherpesvirus that infects chickens and causes the most frequent clinically diagnosed cancer in the animal kingdom. Not only is MDV an important pathogen that threatens the poultry industry but it is also used as a natural virus-host model for herpesvirus-induced tumor formation. In order to visualize MDV-induced lymphoma and to identify potential biomarkers in an unbiased approach, we performed imaging mass spectrometry (IMS) and noncontact laser capture microdissection. This study provides a first description of the visualization of MDV-induced tumors by IMS that could be applied also for diagnostic purposes. In addition, we identified and validated potential biomarkers for MDV-induced tumors that could provide the basis for future research on pathogenesis and tumorigenesis of this malignancy.V. I. PaukerL. D. BertzbachA. HohmannA. KheimarJ. P. TeifkeT. C. MettenleiterA. KargerB. B. KauferAmerican Society for MicrobiologyarticleMarek’s disease virusimaging mass spectrometrylymphomanoncontact laser capture microdissectionproteometumorMicrobiologyQR1-502ENmSphere, Vol 4, Iss 1 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Marek’s disease virus imaging mass spectrometry lymphoma noncontact laser capture microdissection proteome tumor Microbiology QR1-502
spellingShingle	Marek’s disease virus imaging mass spectrometry lymphoma noncontact laser capture microdissection proteome tumor Microbiology QR1-502 V. I. Pauker L. D. Bertzbach A. Hohmann A. Kheimar J. P. Teifke T. C. Mettenleiter A. Karger B. B. Kaufer Imaging Mass Spectrometry and Proteome Analysis of Marek’s Disease Virus-Induced Tumors
description	ABSTRACT The highly oncogenic alphaherpesvirus Marek’s disease virus (MDV) causes immense economic losses in the poultry industry. MDV induces a variety of symptoms in infected chickens, including neurological disorders and immunosuppression. Most notably, MDV induces transformation of lymphocytes, leading to T cell lymphomas in visceral organs with a mortality of up to 100%. While several factors involved in MDV tumorigenesis have been identified, the transformation process and tumor composition remain poorly understood. Here we developed an imaging mass spectrometry (IMS) approach that allows sensitive visualization of MDV-induced lymphoma with a specific mass profile and precise differentiation from the surrounding tissue. To identify potential tumor markers in tumors derived from a very virulent wild-type virus and a telomerase RNA-deficient mutant, we performed laser capture microdissection (LCM) and thereby obtained tumor samples with no or minimal contamination from surrounding nontumor tissue. The proteomes of the LCM samples were subsequently analyzed by quantitative mass spectrometry based on stable isotope labeling. Several proteins, like interferon gamma-inducible protein 30 and a 70-kDa heat shock protein, were identified that are differentially expressed in tumor tissue compared to surrounding tissue and naive T cells. Taken together, our results demonstrate for the first time that MDV-induced tumors can be visualized using IMS, and we identified potential MDV tumor markers by analyzing the proteomes of virus-induced tumors. IMPORTANCE Marek’s disease virus (MDV) is an oncogenic alphaherpesvirus that infects chickens and causes the most frequent clinically diagnosed cancer in the animal kingdom. Not only is MDV an important pathogen that threatens the poultry industry but it is also used as a natural virus-host model for herpesvirus-induced tumor formation. In order to visualize MDV-induced lymphoma and to identify potential biomarkers in an unbiased approach, we performed imaging mass spectrometry (IMS) and noncontact laser capture microdissection. This study provides a first description of the visualization of MDV-induced tumors by IMS that could be applied also for diagnostic purposes. In addition, we identified and validated potential biomarkers for MDV-induced tumors that could provide the basis for future research on pathogenesis and tumorigenesis of this malignancy.
format	article
author	V. I. Pauker L. D. Bertzbach A. Hohmann A. Kheimar J. P. Teifke T. C. Mettenleiter A. Karger B. B. Kaufer
author_facet	V. I. Pauker L. D. Bertzbach A. Hohmann A. Kheimar J. P. Teifke T. C. Mettenleiter A. Karger B. B. Kaufer
author_sort	V. I. Pauker
title	Imaging Mass Spectrometry and Proteome Analysis of Marek’s Disease Virus-Induced Tumors
title_short	Imaging Mass Spectrometry and Proteome Analysis of Marek’s Disease Virus-Induced Tumors
title_full	Imaging Mass Spectrometry and Proteome Analysis of Marek’s Disease Virus-Induced Tumors
title_fullStr	Imaging Mass Spectrometry and Proteome Analysis of Marek’s Disease Virus-Induced Tumors
title_full_unstemmed	Imaging Mass Spectrometry and Proteome Analysis of Marek’s Disease Virus-Induced Tumors
title_sort	imaging mass spectrometry and proteome analysis of marek’s disease virus-induced tumors
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/958a24e0223c45028030cb36f8139b84
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Imaging Mass Spectrometry and Proteome Analysis of Marek’s Disease Virus-Induced Tumors

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