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PLoS Pathog. 2014 Feb 27;10(2):e1003917. doi: 10.1371/journal.ppat.1003917. eCollection 2014 Feb.

Gem-induced cytoskeleton remodeling increases cellular migration of HTLV-1-infected cells, formation of infected-to-target T-cell conjugates and viral transmission.

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Equipe Oncogenèse Rétrovirale, Equipe labellisée "Ligue Nationale Contre le Cancer", International Center for Research in Infectiology, INSERM U1111 - CNRS UMR5308, Ecole Normale Supérieure de Lyon, Université Lyon 1, Lyon, France.
Epidémiologie et Physiopathologie des Virus Oncogènes, CNRS UMR 3569, Pasteur Institute, Paris, France.
Virus Tumor Biology Section, Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
Animal Models and Retroviral Vaccine Section, Vaccine Branch, CCR, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.


Efficient HTLV-1 viral transmission occurs through cell-to-cell contacts. The Tax viral transcriptional activator protein facilitates this process. Using a comparative transcriptomic analysis, we recently identified a series of genes up-regulated in HTLV-1 Tax expressing T-lymphocytes. We focused our attention towards genes that are important for cytoskeleton dynamic and thus may possibly modulate cell-to-cell contacts. We first demonstrate that Gem, a member of the small GTP-binding proteins within the Ras superfamily, is expressed both at the RNA and protein levels in Tax-expressing cells and in HTLV-1-infected cell lines. Using a series of ChIP assays, we show that Tax recruits CREB and CREB Binding Protein (CBP) onto a c-AMP Responsive Element (CRE) present in the gem promoter. This CRE sequence is required to drive Tax-activated gem transcription. Since Gem is involved in cytoskeleton remodeling, we investigated its role in infected cells motility. We show that Gem co-localizes with F-actin and is involved both in T-cell spontaneous cell migration as well as chemotaxis in the presence of SDF-1/CXCL12. Importantly, gem knock-down in HTLV-1-infected cells decreases cell migration and conjugate formation. Finally, we demonstrate that Gem plays an important role in cell-to-cell viral transmission.

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