Imperial College London
Alternate

ProfessorCharlesBangham

Institute of Infection

Co-Director of the Institute of Infection
 
 
 
//

Contact

 

+44 (0)20 7594 3730c.bangham Website

 
 
//

Assistant

 

Ms Linda Hollick +44 (0)20 7594 3729

 
//

Location

 

115Wright Fleming WingSt Mary's Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Kiik:2022:10.1371/journal.ppat.1010387,
author = {Kiik, H and Ramanayake, S and Miura, M and Tanaka, Y and Melamed, A and Bangham, CRM},
doi = {10.1371/journal.ppat.1010387},
journal = {PLoS Pathogens},
title = {Time-course of host cell transcription during the HTLV-1 transcriptional burst},
url = {http://dx.doi.org/10.1371/journal.ppat.1010387},
volume = {18},
year = {2022}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The human T-cell leukemia virus type 1 (HTLV-1) transactivator protein Tax has pleiotropic functions in the host cell affecting cell-cycle regulation, DNA damage response pathways and apoptosis. These actions of Tax have been implicated in the persistence and pathogenesis of HTLV-1-infected cells. It is now known that tax expression occurs in transcriptional bursts of the proviral plus-strand, but the effects of the burst on host transcription are not fully understood. We carried out RNA sequencing of two naturally-infected T-cell clones transduced with a Tax-responsive Timer protein, which undergoes a time-dependent shift in fluorescence emission, to study transcriptional changes during successive phases of the HTLV-1 plus-strand burst. We found that the transcriptional regulation of genes involved in the NF-κB pathway, cell-cycle regulation, DNA damage response and apoptosis inhibition were immediate effects accompanying the plus-strand burst, and are limited to the duration of the burst. The results distinguish between the immediate and delayed effects of HTLV-1 reactivation on host transcription, and between clone-specific effects and those observed in both clones. The major transcriptional changes in the infected host T-cells observed here, including NF-κB, are transient, suggesting that these pathways are not persistently activated at high levels in HTLV-1-infected cells. The two clones diverged strongly in their expression of genes regulating the cell cycle. Up-regulation of senescence markers was a delayed effect of the proviral plus-strand burst and the up-regulation of some pro-apoptotic genes outlasted the burst. We found that activation of the aryl hydrocarbon receptor (AhR) pathway enhanced and prolonged the proviral burst, but did not increase the rate of reactivation. Our results also suggest that sustained plus-strand expression is detrimental to the survival of infected cells.
AU  - Kiik,H
AU  - Ramanayake,S
AU  - Miura,M
AU  - Tanaka,Y
AU  - Melamed,A
AU  - Bangham,CRM
DO  - 10.1371/journal.ppat.1010387
PY  - 2022///
SN  - 1553-7366
TI  - Time-course of host cell transcription during the HTLV-1 transcriptional burst
T2  - PLoS Pathogens
UR  - http://dx.doi.org/10.1371/journal.ppat.1010387
UR  - https://www.ncbi.nlm.nih.gov/pubmed/35576236
UR  - http://hdl.handle.net/10044/1/109045
VL  - 18
ER  -
Download