The cellular stress response enhances human T-cell lymphotropic virus type 1 basal gene expression through the core promoter region of the long terminal repeat.
Viral protein expression is postulated to play a critical role in the pathogenesis of human T-cell lymphotropic virus type 1 (HTLV-1)-associated diseases. Therefore, knowledge of the cellular events which initiate or enhance viral gene expression is important in understanding the mechanism of HTLV-1-induced disease. In this report, we examined the modulation of transcription of the HTLV-1 long terminal repeat (LTR) following induction of the cellular stress response. We demonstrate by both in vitro transcription assays and transient transfections that induction of the stress response increases basal transcription from the LTR. Transient cotransfection assays indicate that stress induction of viral transcription is Tax independent. In addition, we provide evidence that the sequences responsible for the enhanced transcription are -52 through +157 of the U3/R region of the HTLV-1 LTR. Finally, our data suggest that the increase in transcription is mediated through an intermediate polymerase II/polymerase III transcriptional complex, demonstrated by the inability to abolish the effect with low concentrations of alpha-amanitin.
Andrews
J M
JM
Center for Retrovirus Research and Department of Veterinary Biosciences, The Ohio State University, Columbus 43210, USA.
Newbound
G C
GC
Oglesbee
M
M
Brady
J N
JN
Lairmore
M D
MD
D000546:Amanitins / Q000494:pharmacology; D018053:Arsenites / Q000494:pharmacology; D002461:Cell Line, Transformed; D017353:Gene Deletion; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D011401:Promoter Regions, Genetic; D012367:RNA, Viral / Q000032:analysis; D012091:Repetitive Sequences, Nucleic Acid; D017670:Sodium Compounds / Q000494:pharmacology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D000546:Amanitins; D018053:Arsenites; D012367:RNA, Viral; D017670:Sodium Compounds; C017947:sodium arsenite