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  • Oral presentation
  • Open Access

Double-stranded RNA adenosine deaminase ADAR1 enhances both T cell susceptibility to human T-cell leukemia virus type 1 and 2 and viral replication

  • 1,
  • 1,
  • 1,
  • 1,
  • 2,
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  • 1Email author
Retrovirology201411 (Suppl 1) :O49

https://doi.org/10.1186/1742-4690-11-S1-O49

  • Published:

Keywords

  • Viral Replication
  • Adenosine Deaminase
  • Cell Susceptibility
  • Transformed Cell Line
  • Antiviral Protein

Type I interferons represent the first line of defense against pathogens. This family of cytokines activates the expression of antiviral proteins, such as the protein kinase R (PKR), an inhibitor of viral mRNA translation, and the double-stranded RNA adenosine deaminase ADAR1. ADAR1 has the ability to convert adenosine (A) into guanosine (G), thereby introducing mutations in the viral genome during its replication. A to G editing was previously reported in cells expressing HTLV-2 or STLV-3 viruses but not investigating in HTLV-1 expressing cells (Ko et al. J. Gen Virol. 2013). Consequently we investigated whether ADAR1 expression was associated or not with an antiviral effect in the course of HTLV-1 and HTLV-2 infections. We first show that ADAR1 expression is increased in ATL patient peripheral blood mononuclear cells, in HTLV-1 and HTLV-2 transformed cell lines as well as in activated primary peripheral blood lymphocytes. Strikingly, in cells transfected with HTLV-1 and HTLV-2 molecular clones, ADAR1 over-expression enhances viral replication and viral egress through PKR functional inhibition, as demonstrated by western-blot analyses, luciferase assays, ELISA and infection experiments. We also demonstrate that this effect is independent of ADAR catalytic activity. In addition, ADAR1 expression enhances the susceptibility of a non-infected T cell line to HTLV-1 and HTLV-2 infection. Altogether, our results demonstrate that an interferon-induced protein exerts a proviral role in the context of HTLV infection by enhancing cells susceptibility to infection and increasing viral replication.

Authors’ Affiliations

(1)
Oncogenèse Rétrovirale, Equipe labellisée Ligue nationale contre le cancer, CIRI, INSERM U1111-CNRS UMR5308, Université Lyon 1, Ecole Normale Supérieure, LabEx ECOFECT - Eco-evolutionary dynamics of infectious diseases, Lyon, Cedex 07, France
(2)
Unité d'Epidémiologie et Physiopathologie des Virus Oncogènes, CNRS URA 3015, Institut Pasteur, Paris, Cedex 15, France

Copyright

© Cachat 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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