HIV-1 protease processes procaspase 8 to cause mitochondrial release of cytochrome c, caspase cleavage and nuclear fragmentation

Z. Nie, B. N. Phenix, J. J. Lum, A. Alam, D. H. Lynch, B. Beckett, P. H. Krammer, R. P. Sekaly, A. D. Badley

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

Infection of T cells with HIV-1 induces apoptosis and modulates apoptosis regulatory molecules. Similar effects occur following treatment of cells with individual HIV-1 encoded proteins. While HIV-1 protease is known to be cytotoxic, little is known of its effect on apoptosis and apoptosis regulatory molecules. The ability of HIV-1 protease to kill cells, coupled with the degenerate substrate specificity of HIV-1 protease, suggests that HIV-1 protease may activate cellular factor(s) which, in turn, induce apoptosis. We demonstrate that HIV-1 protease directly cleaves and activates procaspase 8 in T cells which is associated with cleavage of BID, mitochondrial release of cytochrome c, activation of the downstream caspases 9 and 3, cleavage of DFF and PARP and, eventually, to nuclear condensation and DNA fragmentation that are characteristic of apoptosis. The effect of HIV-1 protease is not seen in T cell extracts which have undetectable levels of procaspase 8, indicating a specificity and requirement for procaspase 8.

Original languageEnglish (US)
Pages (from-to)1172-1184
Number of pages13
JournalCell Death and Differentiation
Volume9
Issue number11
DOIs
StatePublished - Jan 1 2002

Keywords

  • Apoptosis
  • Caspase 8
  • Cytochrome c
  • HIV
  • HIV-1 protease
  • Mitochondrial
  • Pemeability transition pore complex

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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