Open AccessHuman Immunodeficiency Virus Type 1 Protease Cleaves Procaspase 8 In Vivo
Author(s) -
Zilin Nie,
Gary D. Bren,
Stacey R. Vlahakis,
Alicia Algeciras Schimnich,
Jason M. Brenchley,
Sergey Trushin,
Sarah Warren,
David J. Schnepple,
Colin Kovacs,
Mona Loutfy,
Daniel C. Douek,
Andrew D. Badley
Publication year - 2007
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.02798-06
Subject(s) - biology , apoptosis , protease , virology , programmed cell death , caspase , virus , cd8 , bystander effect , immunology , immune system , enzyme , genetics , biochemistry
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.