Induction of Caspase-dependant Apoptosis by Enterovirus 70 in Human Lens Epithelial SRA01/04 Cells
- 1 Louisiana State University Health Sciences Center Shreveport, United States
- 2 Louisiana State University Health Sciences Center Shreveport, United Kingdom
- 3 The University of Southern Mississippi, United States
Abstract
Enterovirus 70 (EV70), an etiological agent of acute hemorrhagic conjunctivitis (AHC), induces apoptosis in human Chang’s conjunctival (HCC) cells. EV70 is also able to infect and replicate in some other human cells such as human lens epithelial SRA01/04 cells and U937 cells. EV70 infection was found to induce apoptosis in SRA01/04 cells. During EV70-induced apoptosis of SRA01/04 cells, the expression levels of procaspase-3, 6 and 7 (all 32kD) were not increased, but procaspase-3 and 7 were activated (cleaved) while the constitutively activated caspase-6 decreased. Z-VD-FMK inhibited EV70-induced apoptosis and extracellular EV70 release, but not intracellular viral production. UV- or heat-inactivated EV70 did not induce apoptosis. Guanidine⋅HCl inhibited EV70 induced apoptosis in a multiple-step viral growth experiment but not in a one-step viral growth experiment. Cycloheximide and high concentration of methoxysuccinyl-Ala-Ala-Pro-Val-chloromethylketone (MPCMK) (0.5 mM) or elastatinal (Ela) (125 mM) also inhibited EV70-induced apoptosis. The results suggest that infectious EV70 is capable of inducing caspase-dependent (especially caspases-3 and 7-dependent) apoptosis in human lens SRA01/04 cells that requires the syntheses of viral proteins, but not viral genome RNA. The results suggest that (a) EV70 protease(s) (2A protease and probably 3C protease) produced during viral replication initiates EV70 induced apoptosis of SRA01/04 cells and (b) EV70 may use similar or same mechanism(s) to induce apoptosis in different human cells such as SRA01/04 and HCC cells.
DOI: https://doi.org/10.3844/ajidsp.2005.90.106
Copyright: © 2005 Dequan Chen, Chris Duggan, Donald E. Texada, Youping Deng, Chanping Liang, Thomas B. Reden and Marlyn P. Langford. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Keywords
- Enterovirus 70
- apoptotic DNA ladder
- APOPercentage dye uptake bioassay
- effector caspase
- caspase-3
- caspase-6
- caspase-7
- caspase inhibitor IX
- 2A protease
- 3C protease