Caspase activation and specific cleavage of substrates after coxsackievirus B3-induced cytopathic effect in HeLa cells

C. M. Carthy, D. J. Granville, K. A. Watson, Daniel R Anderson, J. E. Wilson, D. Yang, D. W C Hunt, B. M. McManus

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

Coxsackievirus B3 (CVB3), an enterovirus in the family Picornaviridae, induces cytopathic changes in cell culture systems and directly injures multiple susceptible organs and tissues in vivo, including the myocardium, early after infection. Biochemical analysis of the cell death pathway in CVB3-infected HeLa cells demonstrated that the 32-kDa proform of caspase 3 is cleaved subsequent to the degenerative morphological changes seen in infected HeLa cells. Caspase activation assays confirm that the cleaved caspase 3 is proteolytically active. The caspase 3 substrates poly(ADP-ribose) polymerase, a DNA repair enzyme, and DNA fragmentation factor, a cytoplasmic inhibitor of an endonuclease responsible for DNA fragmentation, were degraded at 9 h following infection, yielding their characteristic cleavage fragments. Inhibition of caspase activation by benzyloxycarbonyl-Val-Ala-Asp- fluoromethylketone (ZVAD.fmk) did not inhibit the virus-induced cytopathic effect, while inhibition of caspase activation by ZVAD.fmk in control apoptotic cells induced by treatment with the porphyrin photosensitizer benzoporphyrin derivative monoacid ring A and visible light inhibited the apoptotic phenotype. Caspase activation and cleavage of substrates may not be responsible for the characteristic cytopathic effect produced by picornavirus infection yet may be related to late-stage alterations of cellular homeostatic processes and structural integrity.

Original languageEnglish (US)
Pages (from-to)7669-7675
Number of pages7
JournalJournal of virology
Volume72
Issue number9
StatePublished - Aug 26 1998

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Enterovirus
cytopathogenicity
caspases
Caspases
HeLa Cells
caspase-3
Caspase 3
Picornaviridae
DNA fragmentation
DNA Fragmentation
Picornaviridae Infections
infection
cells
DNA Repair Enzymes
NAD ADP-ribosyltransferase
porphyrins
Photosensitizing Agents
Poly(ADP-ribose) Polymerases
Endonucleases
Porphyrins

ASJC Scopus subject areas

  • Immunology

Cite this

Carthy, C. M., Granville, D. J., Watson, K. A., Anderson, D. R., Wilson, J. E., Yang, D., ... McManus, B. M. (1998). Caspase activation and specific cleavage of substrates after coxsackievirus B3-induced cytopathic effect in HeLa cells. Journal of virology, 72(9), 7669-7675.

Caspase activation and specific cleavage of substrates after coxsackievirus B3-induced cytopathic effect in HeLa cells. / Carthy, C. M.; Granville, D. J.; Watson, K. A.; Anderson, Daniel R; Wilson, J. E.; Yang, D.; Hunt, D. W C; McManus, B. M.

In: Journal of virology, Vol. 72, No. 9, 26.08.1998, p. 7669-7675.

Research output: Contribution to journalArticle

Carthy, CM, Granville, DJ, Watson, KA, Anderson, DR, Wilson, JE, Yang, D, Hunt, DWC & McManus, BM 1998, 'Caspase activation and specific cleavage of substrates after coxsackievirus B3-induced cytopathic effect in HeLa cells', Journal of virology, vol. 72, no. 9, pp. 7669-7675.
Carthy, C. M. ; Granville, D. J. ; Watson, K. A. ; Anderson, Daniel R ; Wilson, J. E. ; Yang, D. ; Hunt, D. W C ; McManus, B. M. / Caspase activation and specific cleavage of substrates after coxsackievirus B3-induced cytopathic effect in HeLa cells. In: Journal of virology. 1998 ; Vol. 72, No. 9. pp. 7669-7675.
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