Imperial College London
ANAT MELAMED

ANAT MELAMED

Faculty of Medicine, Department of Infectious Disease

Research Associate
 
 
 
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Contact

 

anat.melamed07

 
 
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Location

 

VD1Medical SchoolSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Niederer:2014:10.1186/1743-422X-11-172,
author = {Niederer, HA and Laydon, DJ and Melamed, A and Elemans, M and Asquith, B and Matsuoka, M and Bangham, CRM},
doi = {10.1186/1743-422X-11-172},
journal = {Virology Journal},
title = {HTLV-1 proviral integration sites differ between asymptomatic carriers and patients with HAM/TSP},
url = {http://dx.doi.org/10.1186/1743-422X-11-172},
volume = {11},
year = {2014}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background: HTLV-1 causes proliferation of clonal populations of infected T cells in vivo, each clone defined by aunique proviral integration site in the host genome. The proviral load is strongly correlated with odds of theinflammatory disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is evidence thatasymptomatic HTLV-1 carriers (ACs) have a more effective CD8 + T cell response, including a higher frequency ofHLA class I alleles able to present peptides from a regulatory protein of HTLV-1, HBZ. We have previously shownthat specific features of the host genome flanking the proviral integration site favour clone survival and spontaneousexpression of the viral transactivator protein Tax in naturally infected PBMCs ex vivo. However, the previous studies werenot designed or powered to detect differences in integration site characteristics between ACs and HAM/TSP patients.Here, we tested the hypothesis that the genomic environment of the provirus differs systematically between ACs andHAM/TSP patients, and between individuals with strong or weak HBZ presentation.Methods: We used our recently described high-throughput protocol to map and quantify integration sites in 95 HAM/TSP patients and 68 ACs from Kagoshima, Japan, and 75 ACs from Kumamoto, Japan. Individuals with 2 or more HLAclass I alleles predicted to bind HBZ peptides were classified ‘strong’ HBZ binders; the remainder were classified ‘weakbinders’.Results: The abundance of HTLV-1-infected T cell clones in vivo was correlated with proviral integration in genes andin areas with epigenetic marks associated with active regulatory elements. In clones of equivalent abundance, integrationsites in genes and active regions were significantly more frequent in ACs than patients with HAM/TSP, irrespectiveof HBZ binding and proviral load. Integration sites in genes were also more frequent in strong HBZ binders than weakHBZ binders.Conclusion: Clonal abundance is correl
AU  - Niederer,HA
AU  - Laydon,DJ
AU  - Melamed,A
AU  - Elemans,M
AU  - Asquith,B
AU  - Matsuoka,M
AU  - Bangham,CRM
DO  - 10.1186/1743-422X-11-172
PY  - 2014///
SN  - 1743-422X
TI  - HTLV-1 proviral integration sites differ between asymptomatic carriers and patients with HAM/TSP
T2  - Virology Journal
UR  - http://dx.doi.org/10.1186/1743-422X-11-172
UR  - http://hdl.handle.net/10044/1/27263
VL  - 11
ER  -
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