Control of cell death pathways by HTLV-1 proteins

Front Biosci (Landmark Ed). 2009 Jan 1;14:3338-51. doi: 10.2741/3456.

Abstract

Individuals infected with HTLV-1 harbor the virus mainly in CD4+ memory T-cells as a lifelong infection that remains subclinical in the majority of cases. However, about 3-5% of HTLV-1-infected individuals develop an aggressive T-cell neoplasia (ATLL) or a neurodegenerative disease (TSP/HAM) after a latency period ranging from years to decades. This review summarizes the current knowledge of the effects of the HTLV-1 proteins Tax, p13 and p12 on cell death and survival pathways. Tax, the major oncogenic determinant of HTLV-1, enhances cell survival through its effects on the NF-kappaB, CREB and AKT pathways and on the tumor suppressors p53 and Rb. p13 is targeted to the inner mitochondrial membrane and sensitizes cells to the Fas/ceramide apoptotic pathway and reactive oxygen species-mediated cell death. p12 enhances release of calcium from the endoplasmic reticulum and therefore may influence calcium-dependent apoptotic signals, including opening of the mitochondrial permeability transition pore. The long-term fate of HTLV-1-infected cells (apoptosis, survival, transformation) may therefore depend on the balance of the effects of Tax, p13 and p12 on cell death pathways.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Death / physiology*
  • Cell Proliferation
  • Cell Survival
  • Homeostasis
  • Human T-lymphotropic virus 1 / metabolism*
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell / pathology*
  • Viral Proteins / physiology*

Substances

  • Viral Proteins