Submitted to: International Congress of Virology
Publication Type: Abstract Only
Publication Acceptance Date: 8/10/1999
Publication Date: N/A
Citation: N/A Interpretive Summary:
Technical Abstract: Apoptosis is an important cellular response in limiting viral infections by specifically killing infected cells. The cell death process is irreversible following the activation of cytoplasmic cysteine proteases (caspases). The caspases are responsible for the degradation of cellular structural and repair proteins as well as activation of other degradative enzymes. Infection of Vero cells with San Miguel sea lion virus serotype (SMSV1) results in the rounding and detachment of cells between 16 to 20 hours post-infection (PI). Cleavage and activation of caspase 3 was detected by Western blotting at 8 hr PI. Cleavage of caspase 3 substrate proteins, PARP and DFF, was also seen at 8 hr PI. Mitochondrial changes (swollen membranes) were visible by electron microscopy at 4 hr PI and were pronounced by 8 hr PI. Mitochondrial damage was facilitated by the cleavage of the cell death antagonist, Bcl-XL, by caspase 3 beginning at 8 hr PI. CPE in SMSV1-infected cells was inhibited by the addition of the generic caspase inhibitor, z-VAD-fmk, and the caspase 3 inhibitor, Ac-DEVD-CMK, in the medium following infection. Inhibitors of caspases 8 and 9 had no effect. These data indicate that caspase 3 plays an important role in the apoptotic process in SMSV1-infected cells.