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Furin-dependent CCL17-fused recombinant toxin controls HTLV-1 infection by targeting and eliminating infected CCR4-expressing cells in vitro and in vivo

Overview of attention for article published in Retrovirology, August 2015
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  • Good Attention Score compared to outputs of the same age (71st percentile)
  • Good Attention Score compared to outputs of the same age and source (72nd percentile)

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7 X users

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Title
Furin-dependent CCL17-fused recombinant toxin controls HTLV-1 infection by targeting and eliminating infected CCR4-expressing cells in vitro and in vivo
Published in
Retrovirology, August 2015
DOI 10.1186/s12977-015-0199-8
Pubmed ID
Authors

Masateru Hiyoshi, Kazu Okuma, Seiji Tateyama, Kazuya Takizawa, Masumichi Saito, Madoka Kuramitsu, Kumiko Araki, Kazuhiro Morishita, Seiji Okada, Naoki Yamamoto, Arya Biragyn, Kazunari Yamaguchi, Isao Hamaguchi

Abstract

Adult T-cell leukemia (ATL) is caused by human T-cell leukemia virus type 1 (HTLV-1) infection. However, there are no therapies to prevent ATL development in high-risk asymptomatic carriers. To develop a therapy targeting HTLV-1-infected cells that are known to express CCR4 frequently, we tested whether truncated Pseudomonas exotoxin (PE38) fused to a CCR4 ligand, CCL17/thymus and activation-regulated chemokine (TARC), selectively eliminates such cells. Our data show that TARC-PE38 efficiently killed HTLV-1-infected cell lines. It also shrank HTLV-1-associated solid tumors in an infected-cell-engrafted mouse model. In HTLV-1-positive humanized mice, TARC-PE38 markedly inhibited the proliferation of HTLV-1-infected human CD4(+)CD25(+) or CD4(+)CD25(+)CCR4(+) cells and reduced the proviral loads (PVLs) in peripheral blood mononuclear cells (PBMCs). Importantly, TARC-PE38 significantly reduced the PVLs in PBMCs obtained from asymptomatic carriers. We show that the cytotoxicity of TARC-PE38 is mediated by the expression of the proprotein convertase, furin. The expression of furin was enhanced in HTLV-1-infected cells and correlated positively with PVLs in HTLV-1-infected individuals, suggesting that infected cells are more susceptible to TARC-PE38 than normal cells. TARC-PE38 robustly controls HTLV-1 infection by eliminating infected cells in both a CCR4- and furin-dependent manner, indicating the excellent therapeutic potential of TARC-PE38.

X Demographics

X Demographics

The data shown below were collected from the profiles of 7 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 16 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Brazil 1 6%
Unknown 15 94%

Demographic breakdown

Readers by professional status Count As %
Researcher 3 19%
Professor 2 13%
Student > Doctoral Student 1 6%
Student > Bachelor 1 6%
Student > Ph. D. Student 1 6%
Other 3 19%
Unknown 5 31%
Readers by discipline Count As %
Medicine and Dentistry 5 31%
Biochemistry, Genetics and Molecular Biology 3 19%
Computer Science 1 6%
Immunology and Microbiology 1 6%
Neuroscience 1 6%
Other 0 0%
Unknown 5 31%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 April 2016.
All research outputs
#6,535,395
of 23,577,654 outputs
Outputs from Retrovirology
#338
of 1,118 outputs
Outputs of similar age
#74,690
of 267,216 outputs
Outputs of similar age from Retrovirology
#6
of 22 outputs
Altmetric has tracked 23,577,654 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 1,118 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.1. This one has gotten more attention than average, scoring higher than 68% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 267,216 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 71% of its contemporaries.
We're also able to compare this research output to 22 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 72% of its contemporaries.