Gem-induced cytoskeleton remodeling increases cellular migration of HTLV-1-infected cells, formation of infected-to-target T-cell conjugates and viral transmission
Author(s)
Type
Journal Article
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.
Date Issued
2014-02-27
Date Acceptance
2013-12-20
Citation
Plos Pathogens, 2014, 10 (2)
ISSN
1553-7374
Publisher
Public Library of Science
Journal / Book Title
Plos Pathogens
Volume
10
Issue
2
Copyright Statement
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for
any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
License URL
Identifier
PII: PPATHOGENS-D-13-01819
Subjects
Cell Line
Chemotaxis, Leukocyte
Chromatin Immunoprecipitation
Cytoskeleton
Fluorescent Antibody Technique
Gene Expression Regulation, Viral
Gene Products, tax
Human T-lymphotropic virus 1
Immunoblotting
Monomeric GTP-Binding Proteins
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocytes
Transcriptional Activation
Transduction, Genetic
Virology
0605 Microbiology
1107 Immunology
1108 Medical Microbiology
Publication Status
Published
Article Number
e1003917