title: Gem-induced cytoskeleton remodeling increases cellular migration of HTLV-1-infected cells, formation of infected-to-target T-cell conjugates and viral transmission.
abstract: 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.
authors.affiliation: 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.
authors.forename: Sébastien A
authors.initials: SA
authors.lastname: Chevalier
authors.affiliation: 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.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Turpin
authors.affiliation: 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.
authors.forename: Anne
authors.initials: A
authors.lastname: Cachat
authors.affiliation: Epidémiologie et Physiopathologie des Virus Oncogènes, CNRS UMR 3569, Pasteur Institute, Paris, France.
authors.forename: Philippe V
authors.initials: PV
authors.lastname: Afonso
authors.affiliation: Epidémiologie et Physiopathologie des Virus Oncogènes, CNRS UMR 3569, Pasteur Institute, Paris, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Gessain
authors.affiliation: Virus Tumor Biology Section, Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: John N
authors.initials: JN
authors.lastname: Brady
authors.affiliation: Animal Models and Retroviral Vaccine Section, Vaccine Branch, CCR, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Pise-Masison
authors.affiliation: 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.
authors.forename: Renaud
authors.initials: R
authors.lastname: Mahieux
mesh_terms: D002460:Cell Line; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D047369:Chromatin Immunoprecipitation; D003599:Cytoskeleton / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D016356:Gene Products, tax / Q000378:metabolism; D015368:Human T-lymphotropic virus 1; D015151:Immunoblotting; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D015533:Transcriptional Activation / Q000502:physiology; D014161:Transduction, Genetic
chemical_list: D016356:Gene Products, tax; C490245:GEM protein, human; D020559:Monomeric GTP-Binding Proteins