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A transgenic Drosophila melanogaster model to study HTLV-I oncoprotein Tax-driven leukemogenesis in vivo

  • Margret Shirinian1,
  • Zakaria Kambris2,
  • Lama Hamadeh1,
  • Chloé Journo3, 4, 5, 6, 7,
  • Caroline Grabbe8,
  • Renaud Mahieux3, 4, 5, 6, 7 and
  • Ali Bazarbachi1, 9Email author
Contributed equally
Retrovirology201512(Suppl 1):O40

Published: 28 August 2015


Transformed Cell LineRNAi LineDrosophila HomologOsteolytic Bone MetastasisCrystalline Array

Adult T-cell Leukemia/Lymphoma is an aggressive malignancy caused by HTLV-1 infection. HTLV-2 is genetically related to HTLV-1, but does not cause a malignant disease. The HTLV-1 Tax (Tax-1) viral transactivator is required for HTLV-1 expression and modulates the classical and non-canonical NF-κB pathways. Interaction of Tax-1 with IKKγ/NEMO results in constitutive activation of NF-κB in HTLV-1 infected cells, and contributes to HTLV-1-driven leukemogenesis. Tax-1 transgenic mice develop leukemia, lymphomas or spontaneous osteolytic bone metastases demonstrating Tax-1 oncogenic properties in vivo. However, the cellular pathways and the partners involved in vivo have not been described. HTLV-2 Tax (Tax-2) has properties different from Tax-1, including different post-translational modifications and different intracellular localization. Thanks to the availability of collection of mutants and RNAi lines, Drosophila melanogaster allows simple and exhaustive genetic screens. We generated transgenic Drosophila models expressing either Tax-1 or Tax-2 in the compound eye and plasmatocytes (leukocyte-like cell). We demonstrate that Tax-1 but not Tax-2 induces a perturbation of the crystalline array of the ommatidia and increase in plasmatocyte proliferation indicating that Tax-1 but not Tax-2 has transforming potential in Drosophila. We further show that induction of the eye phenotype is primarily dependent on Kenny, the Drosophila homolog of IKKγ/NEMO, upstream of Relish (NF-κB) activation. Using this model we were able to identify a novel post-translational modification which Tax-1 undergoes in addition to the well-known ubiquitylation and SUMOylation. This novel Tax post-translational modification was confirmed in HTLV-I transformed cell lines. Altogether, these results show that the Drosophila system is useful for dissecting the molecular mechanisms of HTLV-1-induced cell transformation in vivo.


Authors’ Affiliations

Department of Internal Medicine, Faculty of Medicine, American University of Beirut, Beirut, Lebanon
Department of Biology, American University of Beirut, Beirut, Lebanon
Equipe Oncogenèse Rétrovirale, Lyon, France
Equipe labellisée “Ligue Nationale Contre le Cancer”, Lyon, France
Centre international de recherche en infectiologie, INSERM U1111 -CNRS UMR5308, Lyon, France
INSERM U1111 Ecole Normale Supérieure de Lyon, Lyon, France
Université Lyon 1, LabEx ECOFECT -Eco-evolutionary dynamics of infectious diseases, Lyon, France
Department of Molecular Biology, Umea University, Umea, Sweden
Department of Anatomy, Cell Biology and Physiological Sciences, American University of Beirut, Beirut, Lebanon


© Shirinian et al. 2015

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.