Human immunodeficiency virus type 1 protease cleaves procaspase 8 in vivo

Zilin Nie, Gary D. Bren, Stacey R. Vlahakis, Alicia Algeciras Schimnich, Jason M. Brenchley, Sergey A. Trushin, Sarah Warren, David J. Schnepple, Colin M. Kovacs, Mona R. Loutfy, Daniel C. Douek, Andrew D. Badley

Research output: Contribution to journalArticle

45 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6947-6956
Number of pages10
JournalJournal of virology
Volume81
Issue number13
DOIs
StatePublished - Jul 1 2007

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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  • Cite this

    Nie, Z., Bren, G. D., Vlahakis, S. R., Schimnich, A. A., Brenchley, J. M., Trushin, S. A., Warren, S., Schnepple, D. J., Kovacs, C. M., Loutfy, M. R., Douek, D. C., & Badley, A. D. (2007). Human immunodeficiency virus type 1 protease cleaves procaspase 8 in vivo. Journal of virology, 81(13), 6947-6956. https://doi.org/10.1128/JVI.02798-06