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Human T-Cell Leukemia Virus Type 1: Transition from Latent Infection to Pathogenic Progression and Implications for Molecular Therapy

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Abstract:

HTLV-1 is etiologically implicated with adult T-cell leukemia (ATL) and tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM). Neither of them is curable by presently known therapy. Therefore, both disorders are waiting for novel therapeutic approaches. Developing such approaches requires comprehensive insight into the viral and cellular factors involved in the genesis of these diseases. It is widely accepted that the viral Tax protein plays a key role in initiating the process leading to ATL, as well as in the pathogenesis of TSP/HAM. Therefore, its various activities are attractive targets for novel molecular or/and immunological therapies. This review describes the effects of Tax that confer its oncogenic potential. These effects require a sufficiently high level of Tax protein, whereas shortly after human infection, the virus enters into a latent state in which no or very low viral gene expression and Tax protein can be detected in the infected cells of the virus carriers. This implies that the dormant virus must be activated in order to elevate Tax protein to its effective level. We review here our and others' data suggesting that this activation can be triggered by stressinducing environmental agents and discuss the mechanism of this activation. In addition, we discuss the pathogenic progression following this virus activation and finally we present perspectives for molecular therapeutic approach for HTLV-1 related clinical disorders.





Keywords: ATL; HTLV-1; TSP/HAM; Tax; apoptosis; genetic instability

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/157339406776872843

Affiliations: Department of Microbiology and Immunology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84105, Israel.

Publication date: May 1, 2006

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  • Current Cancer Therapy Reviews publishes frontier reviews on all the latest advances in clinical oncology, cancer therapy and pharmacology. The journal's aim is to publish the highest quality review articles dedicated to clinical research in the field. The journal is essential reading for all researchers and clinicians in cancer therapy.
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