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Herpes simplex virus type-1 infection upregulates cellular promoters and telomerase activity in both tumor and nontumor human cells

Abstract

Targeted gene expression through viral vectors has been a promising approach for gene therapy. However, the effects of viral gene products expressed from virus vectors on the expression of the host gene are not well known. In the present study, we examined the activities of cellular promoters, including the promoter for genes of human telomerase reverse transcriptase (hTERT), tyrosinase and probasin, in both tumor and normal cells after infection with herpes simplex virus type 1 (HSV-1) vectors. Our results showed that infection with replication-defective HSV-1 vectors significantly upregulated the activity of all three cellular promoters in a nonsequence specific fashion in all cell types tested. Furthermore, viral infection upregulated activities of the hTERT promoter and endogenous telomerase in nontumoral cells. Additional experiments suggested that the viral immediate-early gene product, infected cell protein 0, might be responsible for the deregulation of cellular promoter activity and activation of telomerase. Our study alerts to the potential risk of oncogenesis through deregulation of host gene expression, such as the telomerase by viral vectors in normal cells.

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Acknowledgements

We thank Drs J Smiley of University of Alberta, Stephen A Rice of University of Minnesota Medical School, Priscilla A Schaffer of University of Pennsylvania School of Medicine, William Goins of University of Pittsburgh and Paul Johnson of Neurovir Inc. for the HSV-1 mutants used in the present study. We also thank Drs David L Bartlett of National Cancer Institute, Peter O'Hare of Marie Curie Research Institute and Saul Silverstein of Columbia University for providing us the plasmid constructs. This study was supported by the grants from National Science Council, ROC to C-T Yang, Canadian Institute of Health Research to W Jia and the Terry Fox Foundation for W Jia and P Rennie.

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Yang, CT., Song, J., Bu, X. et al. Herpes simplex virus type-1 infection upregulates cellular promoters and telomerase activity in both tumor and nontumor human cells. Gene Ther 10, 1494–1502 (2003). https://doi.org/10.1038/sj.gt.3302005

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