Neoplastic transformation of T lymphocytes through transgenic expression of a virus host modification protein.

Virus host evasion genes are ready-made tools for gene manipulation and therapy. In this work we have assessed the impact in vivo of the evasion gene A238L of the African Swine Fever Virus, a gene which inhibits transcription mediated by both NF-κB and NFAT. The A238L gene has been selectively expre...

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Autores principales:	Sílvia Cristina Paiva Almeida, Vivian Leite de Oliveira, Sónia Ventura, Margarita Bofill, Robert Michael Evans Parkhouse
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/919913ffb40a45f39bb004054ff9f018
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spelling	oai:doaj.org-article:919913ffb40a45f39bb004054ff9f0182021-11-18T07:20:37ZNeoplastic transformation of T lymphocytes through transgenic expression of a virus host modification protein.1932-620310.1371/journal.pone.0034140https://doaj.org/article/919913ffb40a45f39bb004054ff9f0182012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22558084/?tool=EBIhttps://doaj.org/toc/1932-6203Virus host evasion genes are ready-made tools for gene manipulation and therapy. In this work we have assessed the impact in vivo of the evasion gene A238L of the African Swine Fever Virus, a gene which inhibits transcription mediated by both NF-κB and NFAT. The A238L gene has been selectively expressed in mouse T lymphocytes using tissue specific promoter, enhancer and locus control region sequences for CD2. The resulting two independently derived transgenic mice expressed the transgene and developed a metastasic, angiogenic and transplantable CD4(+)CD8(+)CD69(-) lymphoma. The CD4(+)CD8(+)CD69(-) cells also grew vigorously in vitro. The absence of CD69 from the tumour cells suggests that they were derived from T cells at a stage prior to positive selection. In contrast, transgenic mice similarly expressing a mutant A238L, solely inhibiting transcription mediated by NF-κB, were indistinguishable from wild type mice. Expression of Rag1, Rag2, TCRβ-V8.2, CD25, FoxP3, Bcl3, Bcl2 l14, Myc, IL-2, NFAT1 and Itk, by purified CD4(+)CD8(+)CD69(-) thymocytes from A238L transgenic mice was consistent with the phenotype. Similarly evaluated expression profiles of CD4(+)CD8(+) CD69(-) thymocytes from the mutant A238L transgenic mice were comparable to those of wild type mice. These features, together with the demonstration of (mono-)oligoclonality, suggest a transgene-NFAT-dependent transformation yielding a lymphoma with a phenotype reminiscent of some acute lymphoblastic lymphomas.Sílvia Cristina Paiva AlmeidaVivian Leite de OliveiraSónia VenturaMargarita BofillRobert Michael Evans ParkhousePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e34140 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sílvia Cristina Paiva Almeida Vivian Leite de Oliveira Sónia Ventura Margarita Bofill Robert Michael Evans Parkhouse Neoplastic transformation of T lymphocytes through transgenic expression of a virus host modification protein.
description	Virus host evasion genes are ready-made tools for gene manipulation and therapy. In this work we have assessed the impact in vivo of the evasion gene A238L of the African Swine Fever Virus, a gene which inhibits transcription mediated by both NF-κB and NFAT. The A238L gene has been selectively expressed in mouse T lymphocytes using tissue specific promoter, enhancer and locus control region sequences for CD2. The resulting two independently derived transgenic mice expressed the transgene and developed a metastasic, angiogenic and transplantable CD4(+)CD8(+)CD69(-) lymphoma. The CD4(+)CD8(+)CD69(-) cells also grew vigorously in vitro. The absence of CD69 from the tumour cells suggests that they were derived from T cells at a stage prior to positive selection. In contrast, transgenic mice similarly expressing a mutant A238L, solely inhibiting transcription mediated by NF-κB, were indistinguishable from wild type mice. Expression of Rag1, Rag2, TCRβ-V8.2, CD25, FoxP3, Bcl3, Bcl2 l14, Myc, IL-2, NFAT1 and Itk, by purified CD4(+)CD8(+)CD69(-) thymocytes from A238L transgenic mice was consistent with the phenotype. Similarly evaluated expression profiles of CD4(+)CD8(+) CD69(-) thymocytes from the mutant A238L transgenic mice were comparable to those of wild type mice. These features, together with the demonstration of (mono-)oligoclonality, suggest a transgene-NFAT-dependent transformation yielding a lymphoma with a phenotype reminiscent of some acute lymphoblastic lymphomas.
format	article
author	Sílvia Cristina Paiva Almeida Vivian Leite de Oliveira Sónia Ventura Margarita Bofill Robert Michael Evans Parkhouse
author_facet	Sílvia Cristina Paiva Almeida Vivian Leite de Oliveira Sónia Ventura Margarita Bofill Robert Michael Evans Parkhouse
author_sort	Sílvia Cristina Paiva Almeida
title	Neoplastic transformation of T lymphocytes through transgenic expression of a virus host modification protein.
title_short	Neoplastic transformation of T lymphocytes through transgenic expression of a virus host modification protein.
title_full	Neoplastic transformation of T lymphocytes through transgenic expression of a virus host modification protein.
title_fullStr	Neoplastic transformation of T lymphocytes through transgenic expression of a virus host modification protein.
title_full_unstemmed	Neoplastic transformation of T lymphocytes through transgenic expression of a virus host modification protein.
title_sort	neoplastic transformation of t lymphocytes through transgenic expression of a virus host modification protein.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/919913ffb40a45f39bb004054ff9f018
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Neoplastic transformation of T lymphocytes through transgenic expression of a virus host modification protein.

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