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 Arimilli, S.
Right arrow Articles by Parks, G. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Arimilli, S.
Right arrow Articles by Parks, G. D.

 Previous Article  |  Next Article 

Journal of Virology, April 2006, p. 3416-3427, Vol. 80, No. 7
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.7.3416-3427.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

A Simian Virus 5 (SV5) P/V Mutant Is Less Cytopathic than Wild-Type SV5 in Human Dendritic Cells and Is a More Effective Activator of Dendritic Cell Maturation and Function

Subhashini Arimilli, Martha A. Alexander-Miller, and Griffith D. Parks*

Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1064

Received 13 September 2005/ Accepted 10 January 2006

Human epithelial cells infected with the parainfluenza virus simian virus 5 (SV5) show minimal activation of host cell interferon (IFN), cytokine, and cell death pathways. In contrast, a recombinant SV5 P/V gene mutant (rSV5-P/V-CPI–) overexpresses viral gene products and is a potent inducer of IFN, proinflammatory cytokines, and apoptosis in these cells. In this study, we have compared the outcomes of wild-type (WT) SV5 and rSV5-P/V-CPI– infections of primary human dendritic cells (DC), important antigen-presenting cells for initiating adaptive immune responses. We have tested the hypothesis that a P/V mutant which activates host antiviral responses will be a more potent inducer of DC maturation and function than WT rSV5, which suppresses host cell responses. Infection of peripheral blood mononuclear cell-derived immature DC with WT rSV5 resulted in high levels of viral protein and progeny virus but very little increase in cell surface costimulatory molecules or secretion of IFN and proinflammatory cytokines. In contrast, immature DC infected with the rSV5-P/V-CPI– mutant produced only low levels of viral protein and progeny virus, but these infected cells were induced to secrete IFN-{alpha} and other cytokines and showed elevated levels of maturation markers. Unexpectedly, DC infected with WT rSV5 showed extensive cytopathic effects and increased levels of active caspase-3, while infection of DC with the P/V mutant was largely noncytopathic. In mixed-culture assays, WT rSV5-infected DC were impaired in the ability to stimulate proliferation of autologous CD4+ T cells, whereas DC infected with the P/V mutant were very effective at activating T-cell proliferation. The addition of a pancaspase inhibitor to DC infected with WT rSV5 reduced cytopathic effects and resulted in higher surface expression levels of maturation markers. Our finding that the SV5 P/V mutant has both a reduced cytopathic effect in human DC compared to WT SV5 and an enhanced ability to induce DC function has implications for the rational design of novel recombinant paramyxovirus vectors based on engineered mutations in the viral P/V gene.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157-1064. Phone: (336) 716-9083. Fax: (336) 716-9928. E-mail: gparks{at}wfubmc.edu.

Journal of Virology, April 2006, p. 3416-3427, Vol. 80, No. 7
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.7.3416-3427.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Arimilli, S., Johnson, J. B., Clark, K. M., Graff, A. H., Alexander-Miller, M. A., Mizel, S. B., Parks, G. D. (2008). Engineered Expression of the TLR5 Ligand Flagellin Enhances Paramyxovirus Activation of Human Dendritic Cell Function. J. Virol. 82: 10975-10985 [Abstract] [Full Text]  
  • Ahmed, M., Marino, T. R., Puckett, S., Kock, N. D., Lyles, D. S. (2008). Immune Response in the Absence of Neurovirulence in Mice Infected with M Protein Mutant Vesicular Stomatitis Virus. J. Virol. 82: 9273-9277 [Abstract] [Full Text]  
  • Munir, S., Le Nouen, C., Luongo, C., Buchholz, U. J., Collins, P. L., Bukreyev, A. (2008). Nonstructural Proteins 1 and 2 of Respiratory Syncytial Virus Suppress Maturation of Human Dendritic Cells. J. Virol. 82: 8780-8796 [Abstract] [Full Text]  
  • Wykosky, J., Gibo, D. M., Debinski, W. (2007). A novel, potent, and specific ephrinA1-based cytotoxin against EphA2 receptor expressing tumor cells. Molecular Cancer Therapeutics 6: 3208-3218 [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]  
  • 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]  
  • Bukreyev, A., Skiadopoulos, M. H., Murphy, B. R., Collins, P. L. (2006). Nonsegmented negative-strand viruses as vaccine vectors.. J. Virol. 80: 10293-10306 [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»