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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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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. |
format | Online Article Text |
id | pubmed-3338727 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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