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 Sun, M.
Right arrow Articles by He, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sun, M.
Right arrow Articles by He, B.

 Previous Article  |  Next Article 

Journal of Virology, May 2004, p. 5068-5078, Vol. 78, No. 10
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.10.5068-5078.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Conserved Cysteine-Rich Domain of Paramyxovirus Simian Virus 5 V Protein Plays an Important Role in Blocking Apoptosis

Minghao Sun,1 Terri A. Rothermel,1 Laurie Shuman,1,2 Jason A. Aligo,1,3 Shibo Xu, Yuan Lin,1 Robert A. Lamb,4 and Biao He1,2,3*

Department of Veterinary Science,1 Graduate Program in Immunobiology, The Huck Institute for Life Sciences,2 Intercollege Graduate Program in Genetics, Pennsylvania State University, University Park, Pennsylvania 16802,3 Howard Hughes Medical Institute, Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 602084

Received 9 September 2003/ Accepted 26 January 2004

The paramyxovirus family includes many well-known human and animal pathogens as well as emerging viruses such as Hendra virus and Nipah virus. The V protein of simian virus 5 (SV5), a prototype of the paramyxoviruses, contains a cysteine-rich C-terminal domain which is conserved among all paramyxovirus V proteins. The V protein can block both interferon (IFN) signaling by causing degradation of STAT1 and IFN production by blocking IRF-3 nuclear import. Previously, it was reported that recombinant SV5 lacking the C terminus of the V protein (rSV5V{Delta}C) induces a severe cytopathic effect (CPE) in tissue culture whereas wild-type (wt) SV5 infection does not induce CPE. In this study, the nature of the CPE and the mechanism of the induction of CPE were investigated. Through the use of DNA fragmentation, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling, and propidium iodide staining assays, it was shown that rSV5V{Delta}C induced apoptosis. Expression of wt V protein prevented apoptosis induced by rSV5V{Delta}C, suggesting that the V protein has an antiapoptotic function. Interestingly, rSV5V{Delta}C induced apoptosis in U3A cells (a STAT1-deficient cell line) and in the presence of neutralizing antibody against IFN, suggesting that the induction of apoptosis by rSV5V{Delta}C was independent of IFN and IFN-signaling pathways. Apoptosis induced by rSV5V{Delta}C was blocked by a general caspase inhibitor, Z-VAD-FMK, but not by specific inhibitors against caspases 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 13, suggesting that rSV5V{Delta}C-induced apoptosis can occur in a caspase 12-dependent manner. Endoplasmic reticulum stress can lead to activation of caspase 12; compared to the results seen with mock and wt SV5 infection, rSV5V{Delta}C infection induced ER stress, as demonstrated by increased expression levels of known ER stress indicators GRP 78, GRP 94, and GADD153. These data suggest that rSV5V{Delta}C can trigger cell death by inducing ER stress.

* Corresponding author. Mailing address: Department of Veterinary Science, Pennsylvania State University, 115 Henning Bldg., University Park, PA 16802. Phone: (814) 863-8533. Fax: (814) 863-6140. E-mail: bxh40{at}psu.edu.

Journal of Virology, May 2004, p. 5068-5078, Vol. 78, No. 10
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.10.5068-5078.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Pillet, S., von Messling, V. (2009). Canine Distemper Virus Selectively Inhibits Apoptosis Progression in Infected Immune Cells. J. Virol. 83: 6279-6287 [Abstract] [Full Text]  
  • Gainey, M. D., Manuse, M. J., Parks, G. D. (2008). A Hyperfusogenic F Protein Enhances the Oncolytic Potency of a Paramyxovirus Simian Virus 5 P/V Mutant without Compromising Sensitivity to Type I Interferon. J. Virol. 82: 9369-9380 [Abstract] [Full Text]  
  • Timani, K. A., Sun, D., Sun, M., Keim, C., Lin, Y., Schmitt, P. T., Schmitt, A. P., He, B. (2008). A Single Amino Acid Residue Change in the P Protein of Parainfluenza Virus 5 Elevates Viral Gene Expression. J. Virol. 82: 9123-9133 [Abstract] [Full Text]  
  • Sun, M., Fuentes, S. M., Timani, K., Sun, D., Murphy, C., Lin, Y., August, A., Teng, M. N., He, B. (2008). Akt Plays a Critical Role in Replication of Nonsegmented Negative-Stranded RNA Viruses. J. Virol. 82: 105-114 [Abstract] [Full Text]  
  • Dillon, P. J., Parks, G. D. (2007). Role for the Phosphoprotein P Subunit of the Paramyxovirus Polymerase in Limiting Induction of Host Cell Antiviral Responses. J. Virol. 81: 11116-11127 [Abstract] [Full Text]  
  • Zalewska, B., Stangret, J., Bury, K., Wojciechowski, M., Kur, J., Piatek, R. (2007). DAF- and collagen-binding properties of chimeric Dr fimbriae. Microbiology 153: 2733-2742 [Abstract] [Full Text]  
  • Dillon, P. J., Wansley, E. K., Young, V. A., Alexander-Miller, M. A., Parks, G. D. (2006). Exchange of P/V genes between two non-cytopathic simian virus 5 variants results in a recombinant virus that kills cells through death pathways that are sensitive to caspase inhibitors. J. Gen. Virol. 87: 3643-3648 [Abstract] [Full Text]  
  • Cruz, C. D., Palosaari, H., Parisien, J.-P., Devaux, P., Cattaneo, R., Ouchi, T., Horvath, C. M. (2006). Measles Virus V Protein Inhibits p53 Family Member p73.. J. Virol. 80: 5644-5650 [Abstract] [Full Text]  
  • Kostyak, J. C., Hunter, J. C., Korzick, D. H. (2006). Acute PKC{delta} inhibition limits ischaemia-reperfusion injury in the aged rat heart: Role of GSK-3{beta}. Cardiovasc Res 70: 325-334 [Abstract] [Full Text]  
  • Nishio, M., Tsurudome, M., Ito, M., Ito, Y. (2005). Human Parainfluenza Virus Type 4 Is Incapable of Evading the Interferon-Induced Antiviral Effect. J. Virol. 79: 14756-14768 [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»