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Molecular Pathology of HTLV-1

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Front. Microbiol. | doi: 10.3389/fmicb.2018.00285

HTLV deregulation of the NF-κB pathway: an update on Tax and antisense proteins role.

  • 1Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Italy

Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL), an aggressive CD4+/CD25+ T-cell malignancy and of a severe neurodegenerative disease, HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). The chronic activation or deregulation of the canonical and non-canonical nuclear factor kappa B (NF-κB) pathways play a crucial role in tumorigenesis. The HTLV-1 Tax-1 oncoprotein is a potent activator of the NF-κB transcription factors and the NF-κB response is required for promoting the development of HTLV-1 transformed cell lines. The homologous retrovirus HTLV-2, which also expresses a Tax-2 transforming protein, is not associated with ATL. In this review, we provide an updated synopsis of the role of Tax-1 in the deregulation of the NF-κB pathway, highlighting the differences with the homologous Tax-2. Special emphasis is directed towards the understanding of the molecular mechanisms involved in NF-κB activation resulting from Tax interaction with host factors affecting several cellular processes, such as cell cycle, apoptosis, senescence, cell proliferation, autophagy, and post-translational modifications. We also discuss the current knowledge on the role of the antisense viral protein HBZ in down-regulating the NF-κB activation induced by Tax, and its implication in cellular senescence. In addition, we review the recent studies on the mechanism of HBZ-mediated inhibition of NF-κB activity as compared to that exerted by the HTLV-2 antisense protein, APH-2. Finally, we discuss recent advances aimed at understanding the role exerted in the development of ATL by the perturbation of NF-κB pathway by viral regulatory proteins.

Keywords: HTLV, tax, NF-kB, HBZ, APH-2, ATL, Cell Proliferation, Apoptosis

Received: 18 Dec 2017; Accepted: 07 Feb 2018.

Edited by:

Hirofumi Akari, Primate Research Institute, Kyoto University, Japan

Reviewed by:

Antonio C. Vallinoto, Institute of Biological Sciences (ICB) of Federal University of Pará, Brazil
Jun-ichirou Yasunaga, Kyoto University, Japan  

Copyright: © 2018 Fochi, Mutascio, Bertazzoni, Zipeto and Romanelli. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Maria G. Romanelli, University of Verona, Department of Neurosciences, Biomedicine and Movement Sciences, Strada le Grazie 8, Verona, 37134, Italy, mariagrazia.romanelli@univr.it