This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Carthy, C. M.
Right arrow Articles by McManus, B. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Carthy, C. M.
Right arrow Articles by McManus, B. M.

 Previous Article  |  Next Article 

Journal of Virology, September 1998, p. 7669-7675, Vol. 72, No. 9
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Caspase Activation and Specific Cleavage of Substrates after Coxsackievirus B3-Induced Cytopathic Effect in HeLa Cells

Christopher M. Carthy,1 David J. Granville,1,2 Kathleen A. Watson,1 Daniel R. Anderson,1,3 Janet E. Wilson,1 Decheng Yang,1 David W. C. Hunt,1,2 and Bruce M. McManus1,*

Department of Pathology and Laboratory Medicine, University of British Columbia---St. Paul's Hospital,1 and QLT PhotoTherapeutics Inc.,2 Vancouver, British Columbia, Canada, and Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska3

Received 9 January 1998/Accepted 21 May 1998

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.

* Corresponding author. Mailing address: Department of Pathology and Laboratory Medicine, Cardiovascular Research Laboratory, University of British Columbia, St. Paul's Hospital, 1081 Burrard St., Vancouver, B.C., Canada V6Z 1Y6. Phone: (604) 631-5200. Fax: (604) 631-5208. E-mail: mcmanus{at}unixg.ubc.ca.

Journal of Virology, September 1998, p. 7669-7675, Vol. 72, No. 9
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Lidsky, P. V., Romanova, L. I., Kolesnikova, M. S., Bardina, M. V., Khitrina, E. V., Hato, S. V., van Kuppeveld, F. J. M., Agol, V. I. (2009). Interactions between Viral and Prokaryotic Pathogens in a Mixed Infection with Cardiovirus and Mycoplasma. J. Virol. 83: 9940-9951 [Abstract] [Full Text]  
  • Romanova, L. I., Lidsky, P. V., Kolesnikova, M. S., Fominykh, K. V., Gmyl, A. P., Sheval, E. V., Hato, S. V., van Kuppeveld, F. J. M., Agol, V. I. (2009). Antiapoptotic Activity of the Cardiovirus Leader Protein, a Viral "Security" Protein. J. Virol. 83: 7273-7284 [Abstract] [Full Text]  
  • Tomasicchio, M., Venter, P. A., H. J. Gordon, K., N. Hanzlik, T., Dorrington, R. A. (2007). Induction of apoptosis in Saccharomyces cerevisiae results in the spontaneous maturation of tetravirus procapsids in vivo. J. Gen. Virol. 88: 1576-1582 [Abstract] [Full Text]  
  • Zaragoza, C., Saura, M., Padalko, E. Y., Lopez-Rivera, E., Lizarbe, T. R., Lamas, S., Lowenstein, C. J. (2006). Viral protease cleavage of inhibitor of {kappa}B{alpha} triggers host cell apoptosis. Proc. Natl. Acad. Sci. USA 103: 19051-19056 [Abstract] [Full Text]  
  • Esfandiarei, M., Suarez, A., Amaral, A., Si, X., Rahmani, M., Dedhar, S., McManus, B. M. (2006). Novel Role for Integrin-Linked Kinase in Modulation of Coxsackievirus B3 Replication and Virus-Induced Cardiomyocyte Injury. Circ. Res. 99: 354-361 [Abstract] [Full Text]  
  • Si, X., Luo, H., Morgan, A., Zhang, J., Wong, J., Yuan, J., Esfandiarei, M., Gao, G., Cheung, C., McManus, B. M. (2005). Stress-Activated Protein Kinases Are Involved in Coxsackievirus B3 Viral Progeny Release. J. Virol. 79: 13875-13881 [Abstract] [Full Text]  
  • Wiegand, M., Bossow, S., Neubert, W. J. (2005). Sendai virus trailer RNA simultaneously blocks two apoptosis-inducing mechanisms in a cell type-dependent manner. J. Gen. Virol. 86: 2305-2314 [Abstract] [Full Text]  
  • Zhang, H. M., Yuan, J., Cheung, P., Chau, D., Wong, B. W., McManus, B. M., Yang, D. (2005). Gamma Interferon-Inducible Protein 10 Induces HeLa Cell Apoptosis through a p53-Dependent Pathway Initiated by Suppression of Human Papillomavirus Type 18 E6 and E7 Expression. Mol. Cell. Biol. 25: 6247-6258 [Abstract] [Full Text]  
  • Si, X., McManus, B. M., Zhang, J., Yuan, J., Cheung, C., Esfandiarei, M., Suarez, A., Morgan, A., Luo, H. (2005). Pyrrolidine Dithiocarbamate Reduces Coxsackievirus B3 Replication through Inhibition of the Ubiquitin-Proteasome Pathway. J. Virol. 79: 8014-8023 [Abstract] [Full Text]  
  • Kim, S.-M., Park, J.-H., Chung, S.-K., Kim, J.-Y., Hwang, H.-Y., Chung, K.-C., Jo, I., Park, S.-I., Nam, J.-H. (2004). Coxsackievirus B3 Infection Induces cyr61 Activation via JNK To Mediate Cell Death. J. Virol. 78: 13479-13488 [Abstract] [Full Text]  
  • Ahn, J., Choi, J., Joo, C. H., Seo, I., Kim, D., Yoon, S. Y., Kim, Y. K., Lee, H. (2004). Susceptibility of mouse primary cortical neuronal cells to coxsackievirus B. J. Gen. Virol. 85: 1555-1564 [Abstract] [Full Text]  
  • Cooray, S. (2004). The pivotal role of phosphatidylinositol 3-kinase-Akt signal transduction in virus survival. J. Gen. Virol. 85: 1065-1076 [Abstract] [Full Text]  
  • Campanella, M., de Jong, A. S., Lanke, K. W. H., Melchers, W. J. G., Willems, P. H. G. M., Pinton, P., Rizzuto, R., van Kuppeveld, F. J. M. (2004). The Coxsackievirus 2B Protein Suppresses Apoptotic Host Cell Responses by Manipulating Intracellular Ca2+ Homeostasis. J. Biol. Chem. 279: 18440-18450 [Abstract] [Full Text]  
  • Esfandiarei, M., Luo, H., Yanagawa, B., Suarez, A., Dabiri, D., Zhang, J., McManus, B. M. (2004). Protein Kinase B/Akt Regulates Coxsackievirus B3 Replication through a Mechanism Which Is Not Caspase Dependent. J. Virol. 78: 4289-4298 [Abstract] [Full Text]  
  • Zhang, H. M., Yuan, J., Cheung, P., Luo, H., Yanagawa, B., Chau, D., Stephan-Tozy, N., Wong, B. W., Zhang, J., Wilson, J. E., McManus, B. M., Yang, D. (2003). Overexpression of Interferon-{gamma}-inducible GTPase Inhibits Coxsackievirus B3-induced Apoptosis through the Activation of the Phosphatidylinositol 3-Kinase/Akt Pathway and Inhibition of Viral Replication. J. Biol. Chem. 278: 33011-33019 [Abstract] [Full Text]  
  • Luo, H., Zhang, J., Dastvan, F., Yanagawa, B., Reidy, M. A., Zhang, H. M., Yang, D., Wilson, J. E., McManus, B. M. (2002). Ubiquitin-Dependent Proteolysis of Cyclin D1 Is Associated with Coxsackievirus-Induced Cell Growth Arrest. J. Virol. 77: 1-9 [Abstract] [Full Text]  
  • Gosselin, A.-S., Simonin, Y., Guivel-Benhassine, F., Rincheval, V., Vayssiere, J.-L., Mignotte, B., Colbere-Garapin, F., Couderc, T., Blondel, B. (2002). Poliovirus-Induced Apoptosis Is Reduced in Cells Expressing a Mutant CD155 Selected during Persistent Poliovirus Infection in Neuroblastoma Cells. J. Virol. 77: 790-798 [Abstract] [Full Text]  
  • Bitzer, M., Armeanu, S., Prinz, F., Ungerechts, G., Wybranietz, W., Spiegel, M., Bernlohr, C., Cecconi, F., Gregor, M., Neubert, W. J., Schulze-Osthoff, K., Lauer, U. M. (2002). Caspase-8 and Apaf-1-independent Caspase-9 Activation in Sendai Virus-infected Cells. J. Biol. Chem. 277: 29817-29824 [Abstract] [Full Text]  
  • Zhang, H. M., Yanagawa, B., Cheung, P., Luo, H., Yuan, J., Chau, D., Wang, A., Bohunek, L., Wilson, J. E., McManus, B. M., Yang, D. (2002). Nip21 Gene Expression Reduces Coxsackievirus B3 Replication by Promoting Apoptotic Cell Death via a Mitochondria-Dependent Pathway. Circ. Res. 90: 1251-1258 [Abstract] [Full Text]  
  • Kuo, R.-L., Kung, S.-H., Hsu, Y.-Y., Liu, W.-T. (2002). Infection with enterovirus 71 or expression of its 2A protease induces apoptotic cell death. J. Gen. Virol. 83: 1367-1376 [Abstract] [Full Text]  
  • Luo, H., Yanagawa, B., Zhang, J., Luo, Z., Zhang, M., Esfandiarei, M., Carthy, C., Wilson, J. E., Yang, D., McManus, B. M. (2002). Coxsackievirus B3 Replication Is Reduced by Inhibition of the Extracellular Signal-Regulated Kinase (ERK) Signaling Pathway. J. Virol. 76: 3365-3373 [Abstract] [Full Text]  
  • Zamora, M., Marissen, W. E., Lloyd, R. E. (2002). Multiple eIF4GI-Specific Protease Activities Present in Uninfected and Poliovirus-Infected Cells. J. Virol. 76: 165-177 [Abstract] [Full Text]  
  • Peng, T., Sadusky, T., Li, Y., Coulton, G. R., Zhang, H., Archard, L. C. (2001). Altered expression of Bag-1 in Coxsackievirus B3 infected mouse heart. Cardiovasc Res 50: 46-55 [Abstract] [Full Text]  
  • Roberts, L. O., Boxall, A. J., Lewis, L. J., Belsham, G. J., Kass, G. E. N. (2000). Caspases are not involved in the cleavage of translation initiation factor eIF4GI during picornavirus infection. J. Gen. Virol. 81: 1703-1707 [Abstract] [Full Text]  
  • Agol, V. I., Belov, G. A., Bienz, K., Egger, D., Kolesnikova, M. S., Romanova, L. I., Sladkova, L. V., Tolskaya, E. A. (2000). Competing Death Programs in Poliovirus-Infected Cells: Commitment Switch in the Middle of the Infectious Cycle. J. Virol. 74: 5534-5541 [Abstract] [Full Text]  
  • Henke, A., Launhardt, H., Klement, K., Stelzner, A., Zell, R., Munder, T. (2000). Apoptosis in Coxsackievirus B3-Caused Diseases: Interaction between the Capsid Protein VP2 and the Proapoptotic Protein Siva. J. Virol. 74: 4284-4290 [Abstract] [Full Text]  
  • Granville, D. J., Carthy, C. M., Jiang, H., Levy, J. G., McManus, B. M., Matroule, J.-Y., Piette, J., Hunt, D. W. C. (2000). Nuclear factor-kappa B activation by the photochemotherapeutic agent verteporfin. Blood 95: 256-262 [Abstract] [Full Text]  
  • Zaragoza, C., Ocampo, C. J., Saura, M., Bao, C., Leppo, M., Lafond-Walker, A., Thiemann, D. R., Hruban, R., Lowenstein, C. J. (1999). Inducible Nitric Oxide Synthase Protection Against Coxsackievirus Pancreatitis. J. Immunol. 163: 5497-5504 [Abstract] [Full Text]  
  • Granville, D. J., Shaw, J. R., Leong, S., Carthy, C. M., Margaron, P., Hunt, D. W., McManus, B. M. (1999). Release of Cytochrome c, Bax Migration, Bid Cleavage, and Activation of Caspases 2, 3, 6, 7, 8, and 9 during Endothelial Cell Apoptosis. Am. J. Pathol. 155: 1021-1025 [Abstract] [Full Text]  
  • Girard, S., Couderc, T., Destombes, J., Thiesson, D., Delpeyroux, F., Blondel, B. (1999). Poliovirus Induces Apoptosis in the Mouse Central Nervous System. J. Virol. 73: 6066-6072 [Abstract] [Full Text]  
  • Huber, M., Watson, K. A., Selinka, H.-C., Carthy, C. M., Klingel, K., McManus, B. M., Kandolf, R. (1999). Cleavage of RasGAP and Phosphorylation of Mitogen-Activated Protein Kinase in the Course of Coxsackievirus B3 Replication. J. Virol. 73: 3587-3594 [Abstract] [Full Text]  
  • Yang, D., Yu, J., Luo, Z., Carthy, C. M., Wilson, J. E., Liu, Z., McManus, B. M. (1999). Viral Myocarditis : Identification of Five Differentially Expressed Genes in Coxsackievirus B3–Infected Mouse Heart. Circ. Res. 84: 704-712 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»