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Human Immunodeficiency Virus Type 1 Protease Cleaves Procaspase 8 In Vivo

2007; American Society for Microbiology; Volume: 81; Issue: 13 Linguagem: Inglês

10.1128/jvi.02798-06

1098-5514

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

Hepatitis C virus research

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.