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Human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein induces DNA damages through Activation-Induced cytidine Deaminase (AID)

How T cells are transformed by HTLV-1 is still unclear, but it is well accepted that the viral oncoprotein Tax is associated with genomic instability of infected cells. Tax has recently been shown to directly induce, in T cells, the expression of AID (Ishikawa C et al., Carcinogenesis, 2011), a cytidine deaminase whose physiologic expression is usually restricted to B cells, in which it initiates class-switch recombination and somatic hypermutations to reshape the primary antibody repertoire after antigen encounter. It is also well established that AID-mediated mutations outside of immunoglobulin gene locus are involved in the oncogenic transformation of B lymphocytes. Besides its role in B cell lymphomagenesis, AID was recently proposed to play a key role in different human cancers linked to chronic inflammation, or in cancers associated with infectious agents. We first confirmed that both Tax+ and HTLV-1-infected T-cell lines, but not uninfected T cells expressed aid mRNA as well as AID protein. We further demonstrated that, primary CD4+ T cells and MOLT-4 T-cell line transduced with lentiviral vector expressing Tax expressed high level of AID. More importantly, we also observed a high level of aid in splenic T lymphoma cells obtained from HTLV-1-infected humanized Rag2-/-gamma c-/- mice that have developed lymphomas. We demonstrate that AID up-regulation in T cells is associated with DNA damage accumulation. Finally, inhibiting AID expression by small hairpin RNA strategy strongly decreases Tax-induced DNA damages. Altogether our data strongly suggest that AID is involved in DNA damages and genomic instability of HTLV-1-infected T-cells.

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Correspondence to Aurélien Riquet.

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Renaud Mahieux, Madeleine Duc-Dodon contributed equally to this work.

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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 (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

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Riquet, A., Chevalier, S., Villaudy, J. et al. Human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein induces DNA damages through Activation-Induced cytidine Deaminase (AID). Retrovirology 11 (Suppl 1), O45 (2014).

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