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A role for RNA stability in the induction of HTLV-1 expression in chronically-infected CD4+ T cells

Retrovirology201411 (Suppl 1) :P114

https://doi.org/10.1186/1742-4690-11-S1-P114

  • Published:

Keywords

  • Luciferase Reporter
  • HDAC Inhibitor
  • Reporter Plasmid
  • Phorbol Ester
  • mRNA Stability

The pathogenesis of HTLV-1-associated diseases involves complex interactions between HTLV-1 and the infected host, and is dependent on viral replication and gene expression. Previous studies from our laboratory have shown that T cell receptor- and phorbol ester (PMA)-mediated stimulation of chronically infected CD4 T-cells increases the expression of integrated HTLV-1 proviruses. Detailed analysis of HTLV-1 RNA and protein species following PMA treatment of the FS and SP HTLV-1-infected T cells demonstrated rapid induction of tax/rex mRNA peaking prior to other HTLV-1 RNA species. This rapid increase in tax/rex mRNA was associated with markedly enhanced tax/rex mRNA stability. (from 3.5 hr to >24hr in treated cells), while the stability of unspliced or singly spliced HTLV1 RNAs did not increase. PMA treatment also increased RNA transcription. These data contrast with a delayed increase in HTLV-1 RNA transcription following treatment the HDAC inhibitor, SAHA. To further identify the elements and mechanisms responsible for enhanced tax/rex RNA stability, we adapted a luciferase reporter assay in which tax/rex cDNA sequences were linked to the 3’ end of luciferase gene. Increased luciferase activity was observed with this reporter plasmid upon PMA treatment, as compared with a reporter plasmid containing tax antisense sequences. Our data support a model whereby T cell activation leads to increased HTLV-1 gene expression through increased tax/rex mRNA stability, which in turn results in induction of Tax protein expression, and further activation of HTLV-1 gene expression, and associated changes in cellular gene expression, contributing to increased T cell survival and proliferation and disease.

Authors’ Affiliations

(1)
The Child Health Institute of New Jersey, USA
(2)
The Cancer Institute of New Jersey, USA
(3)
Department of Pharmacology, UMDNJ-RWJMS, New Brunswick, NJ, USA
(4)
Department of Pathology and Laboratory Medicine, UMDNJ-RWJMS, New Brunswick, NJ, USA
(5)
Department of Pediatrics, UMDNJ-RWJMS, New Brunswick, NJ, USA

Copyright

© Lin et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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