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Viruses 2011, 3(11), 2146-2159; doi:10.3390/v3112146
Article

Activation of LTRs from Different Human Endogenous Retrovirus (HERV) Families by the HTLV-1 Tax Protein and T-Cell Activators

1,2
,
3
,
4,5
,
1,2
 and
1,2,*
1 Département des sciences biologiques, Université du Québec à Montréal, SB-R860, 2080 St-Urbain, Montréal, Québec, H2X 3X8, Canada 2 Centre de recherche BioMed, Université du Québec à Montréal, SB-R860, 2080 St-Urbain, Montréal, Québec, H2X 3X8, Canada 3 Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA 4 Institute of Virology, Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Virology, 85764 Neuherberg, Germany 5 III. Medizinische Klinik, UMM-Universitätsmedizin Mannheim, University of Heidelberg, 68305 Mannheim, Germany
* Author to whom correspondence should be addressed.
Received: 20 September 2011 / Accepted: 22 October 2011 / Published: 2 November 2011
(This article belongs to the Special Issue Recent Developments in HTLV Research)
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Abstract

Human endogenous retroviruses (HERVs) represent approximately 8% of our genome. HERVs influence cellular gene expression and contribute to normal physiological processes such as cellular differentiation and morphogenesis. HERVs have also been associated with certain pathological conditions, including cancer and neurodegenerative diseases. As HTLV-1 causes adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and has been shown to modulate host gene expression mainly through the expression of the powerful Tax transactivator, herein we were interested in looking at the potential modulation capacity of HTLV-1 Tax on HERV expression. In order to evaluate the promoter activity of different HERV LTRs, pHERV-LTR-luc constructs were co-transfected in Jurkat T-cells with a Tax expression vector. Tax expression potently increased the LTR activity of HERV-W8 and HERV-H (MC16). In parallel, Jurkat cells were also stimulated with different T-cell-activating agents and HERV LTRs were observed to respond to different combination of Forskolin, bpV[pic] a protein tyrosine phosphatase inhibitor, and PMA. Transfection of expression vectors for different Tax mutants in Jurkat cells showed that several transcription factors including CREB appeared to be important for HERV-W8 LTR activation. Deletion mutants were derived from the HERV-W8 LTR and the region from −137 to −123 was found to be important for LTR response following Tax expression in Jurkat cells, while a different region was shown to be required in cells treated with activators. Our results thus demonstrated that HTLV-1 Tax activates several HERV LTRs. This raises the possibility that upregulated HERV expression could be involved in diseases associated with HTLV-1 infection.
Keywords: HTLV-1; HERVs; Tax; CREB HTLV-1; HERVs; Tax; CREB
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Toufaily, C.; Landry, S.; Leib-Mosch, C.; Rassart, E.; Barbeau, B. Activation of LTRs from Different Human Endogenous Retrovirus (HERV) Families by the HTLV-1 Tax Protein and T-Cell Activators. Viruses 2011, 3, 2146-2159.

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