 |
Journal articles
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 cAMP 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.
https://hal-pasteur.archives-ouvertes.fr/pasteur-01380784
Contributor : Philippe Afonso <>
Submitted on : Thursday, October 13, 2016 - 2:47:29 PM
Last modification on : Monday, June 14, 2021 - 11:13:28 AM
Long-term archiving on: : Saturday, February 4, 2017 - 9:32:39 PM
Contributor : Philippe Afonso <>
Submitted on : Thursday, October 13, 2016 - 2:47:29 PM
Last modification on : Monday, June 14, 2021 - 11:13:28 AM
Long-term archiving on: : Saturday, February 4, 2017 - 9:32:39 PM
File
journal.ppat.1003917.PDF
Publisher files allowed on an open archive