African swine fever virus IAP homologue inhibits caspase activation and promotes cell survival in mammalian cells.
African swine fever virus (ASFV) A224L is a member of the inhibitor of apoptosis protein (IAP) family. We have investigated the antiapoptotic function of the viral IAP both in stably transfected cells and in ASFV-infected cells. A224L was able to substantially inhibit caspase activity and cell death induced by treatment with tumor necrosis factor alpha and cycloheximide or staurosporine when overexpressed in Vero cells by gene transfection. We have also observed that ASFV infection induces caspase activation and apoptosis in Vero cells. Furthermore, using a deletion mutant of ASFV lacking the A224L gene, we have shown that the viral IAP modulates the proteolytic processing of the effector cell death protease caspase-3 and the apoptosis which are induced in the infected cells. Our findings indicate that A224L interacts with the proteolytic fragment of caspase-3 and inhibits the activity of this protease during ASFV infection. These observations could indicate a conserved mechanism of action for ASFV IAP and other IAP family members to suppress apoptosis.
Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
M L
ML
Nogal
G
G
González de Buitrago
C
C
Rodríguez
B
B
Cubelos
A L
AL
Carrascosa
M L
ML
Salas
Y
Y
Revilla
D000358:African Swine Fever Virus / Q000235:genetics / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002470:Cell Survival; D002522:Chlorocebus aethiops; D004789:Enzyme Activation; D005434:Flow Cytometry; D017353:Gene Deletion; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins; D011506:Proteins; D014162:Transfection; D014709:Vero Cells; D015678:Viral Structural Proteins / Q000235:genetics / Q000502:physiology*
C097626:A224L protein, African swine fever virus; D001426:Bacterial Proteins; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins; D011506:Proteins; D015678:Viral Structural Proteins; D053148:Caspase 3; D020169:Caspases