Human immunodeficiency virus type 1 protease cleaves procaspase 8 in vivo.
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.
Nie
Zilin
Z
Division of Infectious Diseases, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
Bren
Gary D
GD
Vlahakis
Stacey R
SR
Schimnich
Alicia Algeciras
AA
Brenchley
Jason M
JM
Trushin
Sergey A
SA
Warren
Sarah
S
Schnepple
David J
DJ
Kovacs
Colin M
CM
Loutfy
Mona R
MR
Douek
Daniel C
DC
Badley
Andrew D
AD
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
D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C505530:CASP8 protein, human; D053181:Caspase 8; D016333:HIV Protease