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{Furuta:2017:10.1371/journal.ppat.1006722,
author = {Furuta, R and Yasunaga, J-I and Miura, M and Sugata, K and Saito, A and Akari, H and Ueno, T and Takenouchi, N and Fujisawa, J-I and Koh, K-R and Higuchi, Y and Mahgoub, M and Shimizu, M and Matsuda, F and Melamed, A and Bangham, CR and Matsuoka, M},
doi = {10.1371/journal.ppat.1006722},
journal = {PLoS Pathogens},
title = {Human T-cell leukemia virus type 1 infects multiple lineage hematopoietic cells in vivo.},
url = {http://dx.doi.org/10.1371/journal.ppat.1006722},
volume = {13},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Human T-cell leukemia virus type 1 (HTLV-1) infects mainly CD4+CCR4+ effector/memory T cells in vivo. However, it remains unknown whether HTLV-1 preferentially infects these T cells or this virus converts infected precursor cells to specialized T cells. Expression of viral genes in vivo is critical to study viral replication and proliferation of infected cells. Therefore, we first analyzed viral gene expression in non-human primates naturally infected with simian T-cell leukemia virus type 1 (STLV-1), whose virological attributes closely resemble those of HTLV-1. Although the tax transcript was detected only in certain tissues, Tax expression was much higher in the bone marrow, indicating the possibility of de novo infection. Furthermore, Tax expression of non-T cells was suspected in bone marrow. These data suggest that HTLV-1 infects hematopoietic cells in the bone marrow. To explore the possibility that HTLV-1 infects hematopoietic stem cells (HSCs), we analyzed integration sites of HTLV-1 provirus in various lineages of hematopoietic cells in patients with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and a HTLV-1 carrier using the high-throughput sequencing method. Identical integration sites were detected in neutrophils, monocytes, B cells, CD8+ T cells and CD4+ T cells, indicating that HTLV-1 infects HSCs in vivo. We also detected Tax protein in myeloperoxidase positive neutrophils. Furthermore, dendritic cells differentiated from HTLV-1 infected monocytes caused de novo infection to T cells, indicating that infected monocytes are implicated in viral spreading in vivo. Certain integration sites were re-detected in neutrophils from HAM/TSP patients at different time points, indicating that infected HSCs persist and differentiate in vivo. This study demonstrates that HTLV-1 infects HSCs, and infected stem cells differentiate into diverse cell lineages. These data indicate that infection of HSCs can contribute to the persistence and spread
AU  - Furuta,R
AU  - Yasunaga,J-I
AU  - Miura,M
AU  - Sugata,K
AU  - Saito,A
AU  - Akari,H
AU  - Ueno,T
AU  - Takenouchi,N
AU  - Fujisawa,J-I
AU  - Koh,K-R
AU  - Higuchi,Y
AU  - Mahgoub,M
AU  - Shimizu,M
AU  - Matsuda,F
AU  - Melamed,A
AU  - Bangham,CR
AU  - Matsuoka,M
DO  - 10.1371/journal.ppat.1006722
PY  - 2017///
SN  - 1553-7366
TI  - Human T-cell leukemia virus type 1 infects multiple lineage hematopoietic cells in vivo.
T2  - PLoS Pathogens
UR  - http://dx.doi.org/10.1371/journal.ppat.1006722
UR  - http://hdl.handle.net/10044/1/54340
VL  - 13
ER  -
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