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Journal of Virology, March 2007, p. 2792-2804, Vol. 81, No. 6
0022-538X/07/$08.00+0     doi:10.1128/JVI.01760-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Oncolytic Vesicular Stomatitis Virus Induces Apoptosis via Signaling through PKR, Fas, and Daxx{triangledown}

Daniel F. Gaddy{dagger} and Douglas S. Lyles*

Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157

Received 14 August 2006/ Accepted 18 December 2006

Matrix (M) protein mutants of vesicular stomatitis virus (VSV) are promising oncolytic agents for cancer therapy. Previous research has implicated Fas and PKR in apoptosis induced by other viruses. Here, we show that dominant-negative mutants of Fas and PKR inhibit M protein mutant virus-induced apoptosis. Most previous research has focused on the adapter protein FADD as a necessary transducer of Fas-mediated apoptosis. However, the expression of dominant-negative FADD had little effect on the induction of apoptosis by M protein mutant VSV. Instead, virus-induced apoptosis was inhibited by the expression of a dominant-negative mutant of the adapter protein Daxx. These data indicate that Daxx is more important than FADD for apoptosis induced by M protein mutant VSV. These results show that PKR- and Fas-mediated signaling play important roles in cell death during M protein mutant VSV infection and that Daxx has novel functions in the host response to virus infection by mediating virus-induced apoptosis.

* Corresponding author. Mailing address: Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157. Phone: (336) 716-4237. Fax: (336) 716-7671. E-mail: dlyles{at}wfubmc.edu.

{triangledown} Published ahead of print on 27 December 2006.

{dagger} Present address: Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261.

Journal of Virology, March 2007, p. 2792-2804, Vol. 81, No. 6
0022-538X/07/$08.00+0     doi:10.1128/JVI.01760-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Pearce, A. F., Lyles, D. S. (2009). Vesicular Stomatitis Virus Induces Apoptosis Primarily through Bak Rather than Bax by Inactivating Mcl-1 and Bcl-XL. J. Virol. 83: 9102-9112 [Abstract] [Full Text]  
  • Hu, W., Hofstetter, W., Wei, X., Guo, W., Zhou, Y., Pataer, A., Li, H., Fang, B., Swisher, S. G. (2009). Double-Stranded RNA-Dependent Protein Kinase-Dependent Apoptosis Induction by a Novel Small Compound. J. Pharmacol. Exp. Ther. 328: 866-872 [Abstract] [Full Text]  
  • Pettit Kneller, E. L., Connor, J. H., Lyles, D. S. (2009). hnRNPs Relocalize to the Cytoplasm following Infection with Vesicular Stomatitis Virus. J. Virol. 83: 770-780 [Abstract] [Full Text]  
  • Tumilasci, V. F., Oliere, S., Nguyen, T. L.-A., Shamy, A., Bell, J., Hiscott, J. (2008). Targeting the Apoptotic Pathway with BCL-2 Inhibitors Sensitizes Primary Chronic Lymphocytic Leukemia Cells to Vesicular Stomatitis Virus-Induced Oncolysis. J. Virol. 82: 8487-8499 [Abstract] [Full Text]  
  • Randall, R. E., Goodbourn, S. (2008). Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. J. Gen. Virol. 89: 1-47 [Abstract] [Full Text]  


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