Imperial College London
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Professor David S. Rueda

Faculty of Medicine, Department of Infectious Disease

Chair in Molecular and Cellular Biophysics
 
 
 
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Contact

 

david.rueda Website

 
 
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Location

 

6.12DLMS BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Miura:2019:10.1371/journal.ppat.1008164,
author = {Miura, M and Dey, S and Ramanayake, S and Singh, A and Rueda, DS and Bangham, CRM},
doi = {10.1371/journal.ppat.1008164},
journal = {PLoS Pathogens},
title = {Kinetics of HTLV-1 reactivation from latency quantified by single-molecule RNA FISH and stochastic modelling},
url = {http://dx.doi.org/10.1371/journal.ppat.1008164},
volume = {15},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The human T cell leukemia virus HTLV-1 establishes a persistent infection in vivo in which the viral sense-strand transcription is usually silent at a given time in each cell. However, cellular stress responses trigger the reactivation of HTLV-1, enabling the virus to transmit to a new host cell. Using single-molecule RNA FISH, we measured the kinetics of the HTLV-1 transcriptional reactivation in peripheral blood mononuclear cells (PBMCs) isolated from HTLV-1+ individuals. The abundance of the HTLV-1 sense and antisense transcripts was quantified hourly during incubation of the HTLV-1-infected PBMCs ex vivo. We found that, in each cell, the sense-strand transcription occurs in two distinct phases: the initial low-rate transcription is followed by a phase of rapid transcription. The onset of transcription peaked between 1 and 3 hours after the start of in vitro incubation. The variance in the transcription intensity was similar in polyclonal HTLV-1+ PBMCs (with tens of thousands of distinct provirus insertion sites), and in samples with a single dominant HTLV-1+ clone. A stochastic simulation model was developed to estimate the parameters of HTLV-1 proviral transcription kinetics. In PBMCs from a leukemic subject with one dominant T-cell clone, the model indicated that the average duration of HTLV-1 sense-strand activation by Tax (i.e. the rapid transcription) was less than one hour. HTLV-1 antisense transcription was stable during reactivation of the sense-strand. The antisense transcript HBZ was produced at an average rate of ~0.1 molecules per hour per HTLV-1+ cell; however, between 20% and 70% of HTLV-1-infected cells were HBZ-negative at a given time, the percentage depending on the individual subject. HTLV-1-infected cells are exposed to a range of stresses when they are drawn from the host, which initiate the viral reactivation. We conclude that whereas antisense-strand transcription is stable throughout the stress response, the HTLV-1 sense-strand reactivati
AU  - Miura,M
AU  - Dey,S
AU  - Ramanayake,S
AU  - Singh,A
AU  - Rueda,DS
AU  - Bangham,CRM
DO  - 10.1371/journal.ppat.1008164
PY  - 2019///
SN  - 1553-7366
TI  - Kinetics of HTLV-1 reactivation from latency quantified by single-molecule RNA FISH and stochastic modelling
T2  - PLoS Pathogens
UR  - http://dx.doi.org/10.1371/journal.ppat.1008164
UR  - https://www.ncbi.nlm.nih.gov/pubmed/31738810
UR  - http://hdl.handle.net/10044/1/75124
VL  - 15
ER  -
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