Rhadinovirus vector-derived human telomerase reverse transcriptase expression in primary T cells

• Verfasst von: Toptan, Tuna [VerfasserIn]
• Verfasst von: Ensser, Armin [VerfasserIn]
• Verfasst von: Fickenscher, Helmut [VerfasserIn]
• Titel: Rhadinovirus vector-derived human telomerase reverse transcriptase expression in primary T cells
• Verf.angabe: T Toptan, A Ensser and H Fickenscher
• E-Jahr: 2010
• Jahr: 18 February 2010
• Umfang: 9 S.
• Fussnoten: Gesehen am 28.11.2023
• Titel Quelle: Enthalten in: Gene therapy
• Ort Quelle: London : Nature Publ. Group, 1997
• Jahr Quelle: 2010
• Band/Heft Quelle: 17(2010), 5, Seite 653-661
• ISSN Quelle: 1476-5462
• DOI: doi:10.1038/gt.2010.3
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Gene expression
• Sach-SW: T cells
• Sach-SW: Viral vectors
• K10plus-PPN: 1871456312

Abstract

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.