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 Google Scholar
Google Scholar
Right arrow Articles by Carey, B. L.
Right arrow Articles by Lyles, D. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Carey, B. L.
Right arrow Articles by Lyles, D. S.

 Previous Article  |  Next Article 

Journal of Virology, December 2008, p. 12104-12115, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01508-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Early Steps of the Virus Replication Cycle Are Inhibited in Prostate Cancer Cells Resistant to Oncolytic Vesicular Stomatitis Virus {triangledown}

Brooke L. Carey, Maryam Ahmed, Shelby Puckett, and Douglas S. Lyles*

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

Received 17 July 2008/ Accepted 25 September 2008

Vesicular stomatitis virus (VSV) is currently being studied as a candidate oncolytic virus for tumor therapies due to its potent tumoricidal activity. Previous studies have demonstrated that VSV selectively infects tumor cells due to defects in their antiviral pathways. These defects make them more susceptible to VSV-induced killing than normal cells. However, some cancer cells display differential sensitivity to VSV. Specifically, LNCaP prostate cancer cells are sensitive to infection with VSV, while PC3 prostate cancer cells are relatively resistant to VSV. This suggests that tumor cells vary in the extent to which they develop defects in antiviral pathways and, thus, permit virus replication. The goal of these studies was to identify the step(s) of the viral replication cycle that is inhibited in PC3 cells. Results showed that although attachment of VSV was not significantly different among cell types, penetration was delayed by 10 to 30 min in PC3 cells relative to LNCaP cells. Primary transcription was delayed by 6 to 8 h in PC3 cells relative to LNCaP cells. Similarly, both secondary transcription and viral protein synthesis rates were delayed by about 6 to 8 h. The progressively increasing delay suggests that more than one step is affected in PC3 cells. Analysis of cellular gene expression showed that in contrast to LNCaP cells, PC3 cells constitutively expressed numerous antiviral gene products, which may enhance their resistance to VSV. These data indicate that the use of VSV for oncolytic virus therapy for prostate tumors may require prescreening of tumors for their level of susceptibility.

* 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 1 October 2008.

Journal of Virology, December 2008, p. 12104-12115, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01508-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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