HTLV-1 Tax: Linking transformation, DNA damage and apoptotic T-cell death.
The human T-cell leukemia virus type I (HTLV-1) is the causative agent of adult T-cell leukemia (ATL), an aggressive CD4-positive T-cell neoplasia. The HTLV-1 proto-oncogene Tax, a potent transcriptional activator of cellular and viral genes, is thought to play a pivotal role in the transforming properties of the virus by deregulating intracellular signaling pathways. During the course of HTLV-1 infection, the dysregulation of cell-cycle checkpoints and the suppression of DNA damage repair is tightly linked to the activity of the viral oncoprotein Tax. Tax activity is associated with production of reactive oxygen intermediates (ROS), chromosomal instability and DNA damage, apoptotic cell death and cellular transformation. Changes in the intracellular redox status induced by Tax promote DNA damage. Tax-mediated DNA damage is believed to be essential in initiating the transformation process by subjecting infected T cells to genetic changes that eventually promote the neoplastic state. Apoptosis and immune surveillance would then exert the necessary selection pressure for eliminating the majority of virally infected cells, while escape variants acquiring a mutator phenotype would constitute a subpopulation of genetically altered cells prone to neoplasia. While the potency of Tax-activity seems to be a determining factor for the observed effects, the cooperation of Tax with other viral proteins determines the fate and progression of HTLV-1-infected cells through DNA damage, apoptosis, survival and transformation.
Chlichlia
Katerina
K
Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece. achlichl@mbg.duth.gr
Khazaie
Khashayarsha
K
D000818:Animals; D017209:Apoptosis; D002472:Cell Transformation, Viral; D004249:DNA Damage; D016356:Gene Products, tax / Q000378:metabolism*; D016355:Genes, pX; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000821:virology*; D000090063:Proto-Oncogene Mas; D013601:T-Lymphocytes / Q000166:cytology*
D016356:Gene Products, tax; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C514970:tax protein, Human T-lymphotrophic virus 1