Herpes simplex virus type-1 infection upregulates cellular promoters and telomerase activity in both tumor and nontumor human cells.
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.
Yang
C-T
CT
Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan.
Song
J
J
Bu
X
X
Cong
Y-S
YS
Bacchetti
S
S
Rennie
P
P
Jia
W W-G
WW
D000727:Androgen-Binding Protein / Q000235:genetics; D002460:Cell Line; D004268:DNA-Binding Proteins; D015870:Gene Expression; D015316:Genetic Therapy / Q000009:adverse effects*; D005822:Genetic Vectors / Q000009:adverse effects*; D006367:HeLa Cells; D006561:Herpes Simplex / Q000235:genetics*; D006801:Humans; D014442:Monophenol Monooxygenase / Q000235:genetics; D009857:Oncogenes; D018139:Simplexvirus / Q000235:genetics*; D015163:Superinfection / Q000235:genetics*; D019098:Telomerase / Q000235:genetics; D014161:Transduction, Genetic / Q000379:methods; D014407:Tumor Cells, Cultured
D000727:Androgen-Binding Protein; D004268:DNA-Binding Proteins; C027519:probasin; D014442:Monophenol Monooxygenase; D019098:Telomerase