HTLV-1 propels untransformed CD4 lymphocytes into the cell cycle while protecting CD8 cells from death

J Clin Invest. 2006 Apr;116(4):974-83. doi: 10.1172/JCI27198.


Human T cell leukemia virus type 1 (HTLV-1) infects both CD4+ and CD8+ lymphocytes, yet it induces adult T cell leukemia/lymphoma (ATLL) that is regularly of the CD4+ phenotype. Here we show that in vivo infected CD4+ and CD8+ T cells displayed similar patterns of clonal expansion in carriers without malignancy. Cloned infected cells from individuals without malignancy had a dramatic increase in spontaneous proliferation, which predominated in CD8+ lymphocytes and depended on the amount of tax mRNA. In fact, the clonal expansion of HTLV-1-positive CD8+ and CD4+ lymphocytes relied on 2 distinct mechanisms--infection prevented cell death in the former while recruiting the latter into the cell cycle. Cell cycling, but not apoptosis, depended on the level of viral-encoded tax expression. Infected tax-expressing CD4+ lymphocytes accumulated cellular defects characteristic of genetic instability. Therefore, HTLV-1 infection establishes a preleukemic phenotype that is restricted to CD4+ infected clones.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / virology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / virology*
  • Carrier State / virology
  • Cell Cycle
  • Cell Proliferation
  • Cells, Cultured
  • Female
  • Human T-lymphotropic virus 1 / pathogenicity*
  • Humans
  • Male
  • Middle Aged
  • Preleukemia / metabolism
  • Preleukemia / virology
  • Time Factors