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Transcriptomic analyses reveal that the cellular Gem protein promotes HTLV-1 infected cell migration and viral transmission

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In a previous study, we used gene expression microarrays and functional assays to identify cellular genes whose expression profiles were similarly affected by Tax proteins from all three HTLV subtypes (HTLV-1, HTLV-2 and HTLV-3). We found forty-eight genes up-regulated by all three Tax proteins (Chevalier et al, Plos One, 2012). Among those, Gem, which encodes a member of the Ras GTP-binding proteins superfamily, was strongly up-regulated. Herein, we first show that Gem expression is strongly up-regulated at the protein level not only in Tax-expressing cells, but also in all tested HTLV-infected cell lines and in primary uncultured T lymphocytes isolated from TSP/HAM patients. We then demonstrate that Tax activates transcription from the Gem promoter through the recruitment of CREB and CBP/p300 onto a cAMP Responsive Element (CRE). Gem protein has been shown to regulate reorganization of the cell cytoskeleton. Since efficient transmission of HTLV-1 from infected to uninfected T cells is mediated by cell-cell contacts, whose formation relies on cytoskeletal reorganization, we investigated the impact of Gem expression on cell migration and formation of cell-cell contacts. Our results show that Gem-overexpressing T lymphocytes display an increased spontaneous migration, while Gem-knocked down HTLV-infected cell lines show a strong reduction in their ability to migrate. We also observe that Gem enhances conjugate formation between infected and non-infected T lymphocytes. Altogether, our results indicate that Gem could be essential for the cell-to-cell spread of HTLV.

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Correspondence to Sébastien A Chevalier.

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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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Chevalier, S.A., Pise-Masison, C.A., Gessain, A. et al. Transcriptomic analyses reveal that the cellular Gem protein promotes HTLV-1 infected cell migration and viral transmission. Retrovirology 11, O64 (2014) doi:10.1186/1742-4690-11-S1-O64

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Keywords

  • Cell Migration
  • Transcriptomic Analysis
  • Expression Microarrays
  • Efficient Transmission
  • Viral Transmission