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

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 (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( 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 (Suppl 1), O64 (2014).

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