Imperial College London
Alternate

ProfessorCharlesBangham

Institute of Infection

Co-Director of the Institute of Infection
 
 
 
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Contact

 

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

 
 
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Assistant

 

Ms Linda Hollick +44 (0)20 7594 3729

 
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Location

 

115Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Ramanayake:2022:10.1371/journal.ppat.1010774,
author = {Ramanayake, S and Moulding, DA and Tanaka, Y and Singh, A and Bangham, CRM},
doi = {10.1371/journal.ppat.1010774},
journal = {PLoS Pathogens},
title = {Dynamics and consequences of the HTLV-1 proviral plus-strand burst},
url = {http://dx.doi.org/10.1371/journal.ppat.1010774},
volume = {18},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Expression of the transcriptional transactivator protein Tax, encoded on the proviral plus-strand of human T-cell leukaemia virus type 1 (HTLV-1), is crucial for the replication of the virus, but Tax-expressing cells are rarely detected in fresh blood ex vivo. The dynamics and consequences of the proviral plus-strand transcriptional burst remain insufficiently characterised. We combined time-lapse live-cell imaging, single-cell tracking and mathematical modelling to study the dynamics of Tax expression at single-cell resolution in two naturally-infected, non-malignant T-cell clones transduced with a short-lived enhanced green fluorescent protein (d2EGFP) Tax reporter system. Five different patterns of Tax expression were observed during the 30-hour observation period; the distribution of these patterns differed between the two clones. The mean duration of Tax expression in the two clones was 94 and 417 hours respectively, estimated from mathematical modelling of the experimental data. Tax expression was associated with a transient slowing in cell-cycle progression and proliferation, increased apoptosis, and enhanced activation of the DNA damage response pathways. Longer-term follow-up (14 days) revealed an increase in the proportion of proliferating cells and a decrease in the fraction of apoptotic cells as the cells ceased Tax expression, resulting in a greater net expansion of the initially Tax-positive population. Time-lapse live-cell imaging showed enhanced cell-to-cell adhesion among Tax-expressing cells, and decreased cell motility of Tax-expressing cells at the single-cell level. The results demonstrate the within-clone and between-clone heterogeneity in the dynamics and patterns of HTLV-1 plus-strand transcriptional bursts and the balance of positive and negative consequences of the burst for the host cell.
AU  - Ramanayake,S
AU  - Moulding,DA
AU  - Tanaka,Y
AU  - Singh,A
AU  - Bangham,CRM
DO  - 10.1371/journal.ppat.1010774
PY  - 2022///
SN  - 1553-7366
TI  - Dynamics and consequences of the HTLV-1 proviral plus-strand burst
T2  - PLoS Pathogens
UR  - http://dx.doi.org/10.1371/journal.ppat.1010774
UR  - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000925001600003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
UR  - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1010774
UR  - http://hdl.handle.net/10044/1/109369
VL  - 18
ER  -
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