Imperial College London
Alternate

Dr Becca Asquith

Faculty of Medicine, Department of Infectious Disease

Professor of Mathematical Immunology
 
 
 
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Contact

 

+44 (0)20 7594 3731b.asquith

 
 
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Location

 

112Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Laydon:2020:10.1371/journal.pcbi.1007470,
author = {Laydon, DJ and Sunkara, V and Boelen, L and Bangham, CRM and Asquith, B},
doi = {10.1371/journal.pcbi.1007470},
journal = {PLoS Computational Biology},
title = {The relative contributions of infectious and mitotic spread to HTLV-1 persistence},
url = {http://dx.doi.org/10.1371/journal.pcbi.1007470},
volume = {16},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Human T-lymphotropic virus type-1 (HTLV-1) persists within hosts via infectious spread (de novo infection) and mitotic spread (infected cell proliferation), creating a population structure of multiple clones (infected cell populations with identical genomic proviral integration sites). The relative contributions of infectious and mitotic spread to HTLV-1 persistence are unknown, and will determine the efficacy of different approaches to treatment. The prevailing view is that infectious spread is negligible in HTLV-1 persistence beyond early infection. However, in light of recent high-throughput data on the abundance of HTLV-1 clones, and recent estimates of HTLV-1 clonal diversity that are substantially higher than previously thought (typically between 104 and 105 HTLV-1+ T cell clones in the body of an asymptomatic carrier or patient with HTLV-1-associated myelopathy/tropical spastic paraparesis), ongoing infectious spread during chronic infection remains possible. We estimate the ratio of infectious to mitotic spread using a hybrid model of deterministic and stochastic processes, fitted to previously published HTLV-1 clonal diversity estimates. We investigate the robustness of our estimates using three alternative estimators. We find that, contrary to previous belief, infectious spread persists during chronic infection, even after HTLV-1 proviral load has reached its set point, and we estimate that between 100 and 200 new HTLV-1 clones are created and killed every day. We find broad agreement between all estimators. The risk of HTLV-1-associated malignancy and inflammatory disease is strongly correlated with proviral load, which in turn is correlated with the number of HTLV-1-infected clones, which are created by de novo infection. Our results therefore imply that suppression of de novo infection may reduce the risk of malignant transformation.
AU  - Laydon,DJ
AU  - Sunkara,V
AU  - Boelen,L
AU  - Bangham,CRM
AU  - Asquith,B
DO  - 10.1371/journal.pcbi.1007470
PY  - 2020///
SN  - 1553-734X
TI  - The relative contributions of infectious and mitotic spread to HTLV-1 persistence
T2  - PLoS Computational Biology
UR  - http://dx.doi.org/10.1371/journal.pcbi.1007470
UR  - https://www.ncbi.nlm.nih.gov/pubmed/32941445
UR  - http://hdl.handle.net/10044/1/82815
VL  - 16
ER  -
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