HTLV-1 Tax: Linking transformation, DNA damage and apoptotic T-cell death

Katerina Chlichlia, Khashayarsha Khazaie

Research output: Contribution to journalReview article

40 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)359-365
Number of pages7
JournalChemico-Biological Interactions
Volume188
Issue number2
DOIs
StatePublished - Nov 2010
Externally publishedYes

Fingerprint

Human T-lymphotropic virus 1
T-cells
Cell death
Taxation
DNA Damage
Cell Death
T-Lymphocytes
DNA
Deltaretrovirus Infections
Viruses
Apoptosis
Adult T Cell Leukemia Lymphoma
Chromosomal Instability
Viral Genes
Proto-Oncogenes
Oncogene Proteins
Viral Proteins
Cell Cycle Checkpoints
DNA Repair
Oxidation-Reduction

Keywords

  • Apoptotic cell death
  • DNA damage
  • HTLV-1 Tax
  • Transformation
  • Viral oncogenes

ASJC Scopus subject areas

  • Toxicology
  • Medicine(all)

Cite this

HTLV-1 Tax : Linking transformation, DNA damage and apoptotic T-cell death. / Chlichlia, Katerina; Khazaie, Khashayarsha.

In: Chemico-Biological Interactions, Vol. 188, No. 2, 11.2010, p. 359-365.

Research output: Contribution to journalReview article

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