A Common Live-Attenuated Avian Herpesvirus Vaccine Expresses a Very Potent Oncogene

ABSTRACT Vaccines play a crucial role in the protection of animals and humans from deadly pathogens. The first vaccine that also protected against cancer was developed against the highly oncogenic herpesvirus Marek’s disease virus (MDV). MDV infects chickens and causes severe immunosuppression, neur...

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Autores principales:	Andelé M. Conradie, Luca D. Bertzbach, Nirajan Bhandari, Mark Parcells, Benedikt B. Kaufer
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	vaccine CVI988/Rispens Marek’s disease virus (MDV) tumorigenesis T cell lymphoma cancer Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/1c7afa1932d64863914ca29d9625bc3f
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spelling	oai:doaj.org-article:1c7afa1932d64863914ca29d9625bc3f2021-11-15T15:27:32ZA Common Live-Attenuated Avian Herpesvirus Vaccine Expresses a Very Potent Oncogene10.1128/mSphere.00658-192379-5042https://doaj.org/article/1c7afa1932d64863914ca29d9625bc3f2019-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00658-19https://doaj.org/toc/2379-5042ABSTRACT Vaccines play a crucial role in the protection of animals and humans from deadly pathogens. The first vaccine that also protected against cancer was developed against the highly oncogenic herpesvirus Marek’s disease virus (MDV). MDV infects chickens and causes severe immunosuppression, neurological signs, and fatal lymphomas, a process that requires the viral oncogene, meq. The most frequently used Marek’s disease vaccine is the live-attenuated CVI988/Rispens (CVI) strain, which efficiently protects chickens and prevents tumorigenesis. Intriguingly, CVI expresses at least two isoforms of meq; however, it remains unknown to what extent these isoforms contribute to virus attenuation. In this study, we individually examined the contribution of the two CVI-meq isoforms to the attenuation of the vaccine. We inserted the respective isoforms into a very virulent MDV (strain RB-1B), thereby replacing its original meq gene. Surprisingly, we could demonstrate that the longer isoform of meq strongly enhanced virus-induced pathogenesis and tumorigenesis, indicating that other mutations in the CVI genome contribute to virus attenuation. On the contrary, the shorter isoform completely abrogated pathogenesis, demonstrating that changes in the meq gene can indeed play a key role in virus attenuation. Taken together, our study provides important evidence on attenuation of one of the most frequently used veterinary vaccines worldwide. IMPORTANCE Marek’s disease virus (MDV) is one of several oncogenic herpesviruses and causes fatal lymphomas in chickens. The current “gold standard” vaccine is the live-attenuated MDV strain CVI988/Rispens (CVI), which is widely used and efficiently prevents tumor formation. Intriguingly, CVI expresses two predominant isoforms of the major MDV oncogene meq: one variant with a regular size of meq (Smeq) and one long isoform (Lmeq) harboring an insertion of 180 bp in the transactivation domain. In our study, we could break the long-standing assumption that the Lmeq isoform is an indicator for virus attenuation. Using recombinant viruses that express the different CVI-meq isoforms, we could demonstrate that both isoforms drastically differ in their abilities to promote pathogenesis and tumor formation in infected chickens.Andelé M. ConradieLuca D. BertzbachNirajan BhandariMark ParcellsBenedikt B. KauferAmerican Society for MicrobiologyarticlevaccineCVI988/RispensMarek’s disease virus (MDV)tumorigenesisT cell lymphomacancerMicrobiologyQR1-502ENmSphere, Vol 4, Iss 5 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	vaccine CVI988/Rispens Marek’s disease virus (MDV) tumorigenesis T cell lymphoma cancer Microbiology QR1-502
spellingShingle	vaccine CVI988/Rispens Marek’s disease virus (MDV) tumorigenesis T cell lymphoma cancer Microbiology QR1-502 Andelé M. Conradie Luca D. Bertzbach Nirajan Bhandari Mark Parcells Benedikt B. Kaufer A Common Live-Attenuated Avian Herpesvirus Vaccine Expresses a Very Potent Oncogene
description	ABSTRACT Vaccines play a crucial role in the protection of animals and humans from deadly pathogens. The first vaccine that also protected against cancer was developed against the highly oncogenic herpesvirus Marek’s disease virus (MDV). MDV infects chickens and causes severe immunosuppression, neurological signs, and fatal lymphomas, a process that requires the viral oncogene, meq. The most frequently used Marek’s disease vaccine is the live-attenuated CVI988/Rispens (CVI) strain, which efficiently protects chickens and prevents tumorigenesis. Intriguingly, CVI expresses at least two isoforms of meq; however, it remains unknown to what extent these isoforms contribute to virus attenuation. In this study, we individually examined the contribution of the two CVI-meq isoforms to the attenuation of the vaccine. We inserted the respective isoforms into a very virulent MDV (strain RB-1B), thereby replacing its original meq gene. Surprisingly, we could demonstrate that the longer isoform of meq strongly enhanced virus-induced pathogenesis and tumorigenesis, indicating that other mutations in the CVI genome contribute to virus attenuation. On the contrary, the shorter isoform completely abrogated pathogenesis, demonstrating that changes in the meq gene can indeed play a key role in virus attenuation. Taken together, our study provides important evidence on attenuation of one of the most frequently used veterinary vaccines worldwide. IMPORTANCE Marek’s disease virus (MDV) is one of several oncogenic herpesviruses and causes fatal lymphomas in chickens. The current “gold standard” vaccine is the live-attenuated MDV strain CVI988/Rispens (CVI), which is widely used and efficiently prevents tumor formation. Intriguingly, CVI expresses two predominant isoforms of the major MDV oncogene meq: one variant with a regular size of meq (Smeq) and one long isoform (Lmeq) harboring an insertion of 180 bp in the transactivation domain. In our study, we could break the long-standing assumption that the Lmeq isoform is an indicator for virus attenuation. Using recombinant viruses that express the different CVI-meq isoforms, we could demonstrate that both isoforms drastically differ in their abilities to promote pathogenesis and tumor formation in infected chickens.
format	article
author	Andelé M. Conradie Luca D. Bertzbach Nirajan Bhandari Mark Parcells Benedikt B. Kaufer
author_facet	Andelé M. Conradie Luca D. Bertzbach Nirajan Bhandari Mark Parcells Benedikt B. Kaufer
author_sort	Andelé M. Conradie
title	A Common Live-Attenuated Avian Herpesvirus Vaccine Expresses a Very Potent Oncogene
title_short	A Common Live-Attenuated Avian Herpesvirus Vaccine Expresses a Very Potent Oncogene
title_full	A Common Live-Attenuated Avian Herpesvirus Vaccine Expresses a Very Potent Oncogene
title_fullStr	A Common Live-Attenuated Avian Herpesvirus Vaccine Expresses a Very Potent Oncogene
title_full_unstemmed	A Common Live-Attenuated Avian Herpesvirus Vaccine Expresses a Very Potent Oncogene
title_sort	common live-attenuated avian herpesvirus vaccine expresses a very potent oncogene
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/1c7afa1932d64863914ca29d9625bc3f
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A Common Live-Attenuated Avian Herpesvirus Vaccine Expresses a Very Potent Oncogene

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