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  • Oral presentation
  • Open Access

STLV-1-infected Japanese macaque as a model of HTLV-1 infection

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  • 1Email author
Retrovirology201411 (Suppl 1) :O12

https://doi.org/10.1186/1742-4690-11-S1-O12

  • Published:

Keywords

  • Integration Site
  • Japanese Macaque
  • Proviral Load
  • Clonal Proliferation
  • Suitable Animal Model

Various non-human primates are the natural hosts of simian T-cell leukemia virus type 1 (STLV-1). In the present study, we analyzed Japanese macaques naturally infected with STLV-1, and evaluated them as an animal model for HTLV-1 research. Approximately 60% of individuals in the colony are seropositive for STLV-1. Clonal proliferation of STLV-1+ cells was investigated by massively sequencing the provirus integration sites. We found that some clones proliferated distinctively in monkeys with higher proviral load. T lymphocytes expressing Tax in the peripheral blood were largely CD4+. Notably, one of the monkeys surveyed in this study developed T-cell lymphoma in the brain, indicating that STLV-1 is oncogenic in Japanese macaques. We also assessed the molecular function of STLV-1 Tax and STLV-1 bZIP factor (SBZ). STLV-1 Tax activated NFAT, AP-1, canonical Wnt and canonical NF-kappa B pathways, whereas SBZ suppressed those signaling pathways. SBZ enhanced TGF-beta signaling, but STLV-1 Tax suppressed it. These findings suggest that STLV-1 Tax and SBZ have similar functions to their counterparts of HTLV-1. In addition, we found that administration of anti-CCR4 antibody, which is currently used in Japan for the treatment of ATL patients, efficiently reduced proviral load in STLV-1-infected Japanese macaques. Our study provides the evidence that Japanese macaques naturally infected with STLV-1 correspond to HTLV-1 carriers and are a suitable animal model to investigate the pathogenesis of HTLV-1 and novel therapeutic strategies.

Authors’ Affiliations

(1)
Institute for Virus Research, Kyoto University, Kyoto, Japan

Copyright

© Miura et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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