title: Human immunodeficiency virus type 1 protease cleaves procaspase 8 in vivo.
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.
authors: Division of Infectious Diseases, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
authors: Zilin
authors: Z
authors: Nie
authors: Gary D
authors: GD
authors: Bren
authors: Stacey R
authors: SR
authors: Vlahakis
authors: Alicia Algeciras
authors: AA
authors: Schimnich
authors: Jason M
authors: JM
authors: Brenchley
authors: Sergey A
authors: SA
authors: Trushin
authors: Sarah
authors: S
authors: Warren
authors: David J
authors: DJ
authors: Schnepple
authors: Colin M
authors: CM
authors: Kovacs
authors: Mona R
authors: MR
authors: Loutfy
authors: Daniel C
authors: DC
authors: Douek
authors: Andrew D
authors: AD
authors: Badley
mesh_terms: D017209:Apoptosis / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology / Q000821:virology; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000201:enzymology* / Q000235:genetics; D016333:HIV Protease / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D007156:Immunologic Memory / Q000235:genetics; D019169:Jurkat Cells; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
chemical_list: D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C505530:CASP8 protein, human; D053181:Caspase 8; D016333:HIV Protease