Multiple viral strategies of HTLV-1 for dysregulation of cell growth control

Annu Rev Immunol. 2001;19:475-96. doi: 10.1146/annurev.immunol.19.1.475.


The human T cell leukemia virus-1 (HTLV-1) is a retrovirus that causes adult T cell leukemia (ATL) and neurological disorder, the tropical spastic paraparesis (HAM/TSP). The pathogenesis apparently results from the pleiotropic function of Tax protein, which is a key regulator of viral replication. Tax exerts (a) trans-activation and -repression of transcription of different sets of cellular genes through binding to groups of transcription factors and coactivators, (b) dysregulation of cell cycle through binding to inhibitors of CDK4/6, and (c) inhibition of some tumor suppressor proteins. These effects on a wide variety of cellular targets seem to cooperate in promoting cell proliferation. This is an effective viral strategy to amplify its proviral genome through replication of infected cells; ultimately it results in cell transformation and leukemogenesis.

Publication types

  • Review

MeSH terms

  • Apoptosis
  • CD4-Positive T-Lymphocytes / pathology
  • CD4-Positive T-Lymphocytes / virology
  • Cell Cycle
  • Cell Cycle Proteins / physiology
  • Cell Division
  • Cell Transformation, Viral / physiology*
  • Cyclic AMP Response Element-Binding Protein / physiology
  • DNA-Binding Proteins / physiology
  • Female
  • Gene Expression Regulation, Viral
  • Gene Products, tax / physiology*
  • Genes, pX*
  • Human T-lymphotropic virus 1 / genetics
  • Human T-lymphotropic virus 1 / physiology*
  • Humans
  • I-kappa B Proteins / antagonists & inhibitors
  • Leukemia-Lymphoma, Adult T-Cell / etiology*
  • Leukemia-Lymphoma, Adult T-Cell / genetics
  • Leukemia-Lymphoma, Adult T-Cell / pathology
  • Leukemia-Lymphoma, Adult T-Cell / virology
  • Male
  • Models, Biological
  • NF-kappa B / physiology
  • Neoplastic Stem Cells / pathology
  • Neoplastic Stem Cells / virology
  • Nuclear Proteins / physiology
  • Serum Response Factor
  • Trans-Activators / physiology
  • Transcriptional Activation
  • Tumor Suppressor Protein p53 / physiology
  • Virus Replication


  • Cell Cycle Proteins
  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins
  • Gene Products, tax
  • I-kappa B Proteins
  • NF-kappa B
  • Nuclear Proteins
  • Serum Response Factor
  • Trans-Activators
  • Tumor Suppressor Protein p53