Targeting HTLV-1 activation of NFκB in mouse models and ATLL patients

Viruses. 2011 Jun;3(6):886-900. doi: 10.3390/v3060886. Epub 2011 Jun 21.

Abstract

Of the millions of HTLV-1 infected carriers worldwide, 3-5% will develop an aggressive T-cell neoplasm that is highly refractory to conventional therapy. The virus carries the Tax oncogene which constitutively activates the NFκB pathway. This co-option of signaling through NFκB provides for the HTLV-1 infected cell an escape from cell cycle arrest and apoptosis, a steady source of growth factors, and a mechanism by which the virus can activate its own target cell. Therapies that target the NFκB pathway sensitize adult T-cell leukemia/lymphoma (ATLL) cells to apoptosis. A focus on translational interrogation of NFκB inhibitors in animal models and ATLL patients is needed to advance NFκB-targeted ATLL therapies to the bedside.

Keywords: ATLL therapy; HTLV-1; NFκB; mouse models; tax.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Gene Products, tax / genetics
  • Gene Products, tax / metabolism
  • Human T-lymphotropic virus 1
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell / drug therapy
  • Leukemia-Lymphoma, Adult T-Cell / genetics*
  • Leukemia-Lymphoma, Adult T-Cell / metabolism
  • Leukemia-Lymphoma, Adult T-Cell / virology
  • Mice
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / genetics*
  • NF-kappa B / metabolism
  • Signal Transduction
  • Transcriptional Activation*

Substances

  • Gene Products, tax
  • NF-kappa B
  • tax protein, Human T-lymphotrophic virus 1