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

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.

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Correspondence to Renaud Mahieux.

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

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Cachat, A., Chevalier, S.A., Alais, S. et al. Double-stranded RNA adenosine deaminase ADAR1 enhances both T cell susceptibility to human T-cell leukemia virus type 1 and 2 and viral replication. Retrovirology 11 (Suppl 1), O49 (2014).

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