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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.

Author information

1
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.
2
Epidémiologie et Physiopathologie des Virus Oncogènes, CNRS UMR 3569, Pasteur Institute, Paris, France.
3
Virus Tumor Biology Section, Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
4
Animal Models and Retroviral Vaccine Section, Vaccine Branch, CCR, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.

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.

PMID:
24586148
PMCID:
PMC3937318
DOI:
10.1371/journal.ppat.1003917
[Indexed for MEDLINE]
Free PMC Article
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