Human immunodeficiency virus type 1 protease cleaves procaspase 8 in vivo

J Virol. 2007 Jul;81(13):6947-56. doi: 10.1128/JVI.02798-06. Epub 2007 Apr 18.

Abstract

Human immunodeficiency virus type 1 (HIV-1) infection causes apoptosis of infected CD4 T cells as well as uninfected (bystander) CD4 and CD8 T cells. It remains unknown what signals cause infected cells to die. We demonstrate that HIV-1 protease specifically cleaves procaspase 8 to create a novel fragment termed casp8p41, which independently induces apoptosis. casp8p41 is specific to HIV-1 protease-induced death but not other caspase 8-dependent death stimuli. In HIV-1-infected patients, casp8p41 is detected only in CD4(+) T cells, predominantly in the CD27(+) memory subset, its presence increases with increasing viral load, and it colocalizes with both infected and apoptotic cells. These data indicate that casp8p41 independently induces apoptosis and is a specific product of HIV-1 protease which may contribute to death of HIV-1-infected cells.

Publication types

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

MeSH terms

  • Apoptosis* / genetics
  • CD4-Positive T-Lymphocytes / enzymology*
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / enzymology
  • CD8-Positive T-Lymphocytes / virology
  • Caspase 8 / genetics
  • Caspase 8 / metabolism*
  • HIV Infections / enzymology*
  • HIV Infections / genetics
  • HIV Protease / genetics
  • HIV Protease / metabolism*
  • HIV-1 / enzymology*
  • HIV-1 / genetics
  • Humans
  • Immunologic Memory / genetics
  • Jurkat Cells
  • Tumor Necrosis Factor Receptor Superfamily, Member 7

Substances

  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • CASP8 protein, human
  • Caspase 8
  • HIV Protease