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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: Almeida, Sílvia Cristina Paiva, de Oliveira, Vivian Leite, Ventura, Sónia, Bofill, Margarita, Parkhouse, Robert Michael Evans
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338727/
https://www.ncbi.nlm.nih.gov/pubmed/22558084
http://dx.doi.org/10.1371/journal.pone.0034140
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author Almeida, Sílvia Cristina Paiva
de Oliveira, Vivian Leite
Ventura, Sónia
Bofill, Margarita
Parkhouse, Robert Michael Evans
author_facet Almeida, Sílvia Cristina Paiva
de Oliveira, Vivian Leite
Ventura, Sónia
Bofill, Margarita
Parkhouse, Robert Michael Evans
author_sort Almeida, Sílvia Cristina Paiva
collection PubMed
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.
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spelling pubmed-33387272012-05-03 Neoplastic Transformation of T Lymphocytes through Transgenic Expression of a Virus Host Modification Protein Almeida, Sílvia Cristina Paiva de Oliveira, Vivian Leite Ventura, Sónia Bofill, Margarita Parkhouse, Robert Michael Evans PLoS One Research Article 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. Public Library of Science 2012-04-27 /pmc/articles/PMC3338727/ /pubmed/22558084 http://dx.doi.org/10.1371/journal.pone.0034140 Text en Almeida et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Almeida, Sílvia Cristina Paiva
de Oliveira, Vivian Leite
Ventura, Sónia
Bofill, Margarita
Parkhouse, Robert Michael Evans
Neoplastic Transformation of T Lymphocytes through Transgenic Expression of a Virus Host Modification Protein
title 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_short 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338727/
https://www.ncbi.nlm.nih.gov/pubmed/22558084
http://dx.doi.org/10.1371/journal.pone.0034140
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