Human immunodeficiency virus type 1 protease cleaves procaspase 8 in vivo |
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Authors: | Nie Zilin Bren Gary D Vlahakis Stacey R Schimnich Alicia Algeciras Brenchley Jason M Trushin Sergey A Warren Sarah Schnepple David J Kovacs Colin M Loutfy Mona R Douek Daniel C Badley Andrew D |
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Institution: | Division of Infectious Diseases, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. |
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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. |
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