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- Title
Neoplastic Transformation of T Lymphocytes through Transgenic Expression of a Virus Host Modification Protein.
- Authors
Almeida, Sílvia Cristina Paiva; de Oliveira, Vivian Leite; Ventura, Sónia; Bofill, Margarita; Parkhouse, Robert Michael Evans
- Abstract
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.
- Subjects
TRANSGENIC mice; T cells; CANCER cells; PHENOTYPES; LYMPHOMAS; RETICULOENDOTHELIAL granulomas; IRIDOVIRUSES; AFRICAN swine fever virus
- Publication
PLoS ONE, 2012, Vol 7, Issue 4, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0034140