title: Caspase-3 and -7 mediate apoptosis of human Chang's conjunctival cells induced by enterovirus 70.
abstract: Enterovirus 70 (EV70) is the major etiological agent of acute hemorrhagic conjunctivitis (AHC). EV70 m.o.i.- (multiplicity of infection) and time-dependently induced apoptosis in human Chang's conjunctival (HCC) cells. UV- or heat-inactivated EV70 did not induce apoptosis. EV70-induced apoptosis was inhibited by cycloheximide and methoxysuccinyl-Ala-Ala-Pro-Val-chloromethylketone (MPCMK), but not actinomycin D and guanidine.HCl (although guanidine.HCl inhibited the apoptosis induced by EV70 infection at 0.5 PFU/cell for 18 h). EV70 infection induced activation of caspase-3 and -7 and degradation of the constitutively activated caspase-6. EV70-induced apoptotic DNA ladders and activated caspase-3 and -7, correlated with virus release. Caspase inhibitor IX (Z-VD-FMK) inhibited EV70-induced apoptosis and virus release, but not intracellular viral production. The results suggest that infectious virus and the syntheses of viral proteins especially EV70 proteases, but not viral genome RNA, are required for caspase-3 and -7-mediated EV70-induced apoptosis, and that apoptosis through cell lysis promotes EV70 release from HCC cells.
authors.affiliation: Department of Ophthalmology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932, USA. dequan.chen@irrdallas.org
authors.forename: Dequan
authors.initials: D
authors.lastname: Chen
authors.forename: Donald E
authors.initials: DE
authors.lastname: Texada
authors.forename: Chris
authors.initials: C
authors.lastname: Duggan
authors.forename: Youping
authors.initials: Y
authors.lastname: Deng
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Redens
authors.forename: Marlyn P
authors.initials: MP
authors.lastname: Langford
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D053178:Caspase 6; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D003228:Conjunctiva / Q000166:cytology* / Q000821:virology; D004770:Enterovirus / Q000502:physiology*; D004769:Enterovirus Infections / Q000276:immunology* / Q000473:pathology; D006801:Humans
chemical_list: C505407:CASP3 protein, human; C505514:CASP6 protein, human; D053148:Caspase 3; D053178:Caspase 6; D020169:Caspases