Rhadinovirus vector-derived human telomerase reverse transcriptase expression in primary T cells
The rhadinovirus herpesvirus saimiri (HVS) as a gene delivery vector allows large DNA insertions and long-termed gene expression. In the case of T-cell transduction, such vectors use the viral transformation-associated genes of HVS C488 for T-cell amplification. In this report, we investigated wheth...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
18 February 2010
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| In: |
Gene therapy
Year: 2010, Volume: 17, Issue: 5, Pages: 653-661 |
| ISSN: | 1476-5462 |
| DOI: | 10.1038/gt.2010.3 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/gt.2010.3 Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/gt20103 
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| Author Notes: | T Toptan, A Ensser and H Fickenscher |
| Summary: | The rhadinovirus herpesvirus saimiri (HVS) as a gene delivery vector allows large DNA insertions and long-termed gene expression. In the case of T-cell transduction, such vectors use the viral transformation-associated genes of HVS C488 for T-cell amplification. In this report, we investigated whether the gene for the catalytic telomerase subunit human telomerase reverse transcriptase (hTERT) can substitute for the transformation-associated genes in rhadinoviral T-cell transduction and amplification. By using virus mutants generated by en passant mutagenesis from bacterial artificial chromosomes, we observed a very early and functional transgene expression even by virus mutants without transformation-associated genes. The markers of T-cell transformation by HVS, namely CD2 hyperreactivity, overexpression of interleukin-26, and of the tyrosine kinase Lyn could neither be induced nor enhanced by ectopic hTERT expression. When the viral transformation-associated genes were replaced by the hTERT gene, it was not sufficient for growth transformation, although hTERT was efficiently transduced and functionally expressed by the rhadinovirus vector. Thus, the transformation-associated proteins StpC and Tip are responsible for the T-cell phenotype after transduction by HVS and, additionally, modulate telomerase activity independently of hTERT expression. |
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| Item Description: | Gesehen am 28.11.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1476-5462 |
| DOI: | 10.1038/gt.2010.3 |