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 Faber, M.
Right arrow Articles by Dietzschold, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Faber, M.
Right arrow Articles by Dietzschold, B.

 Previous Article  |  Next Article 

Journal of Virology, April 2002, p. 3374-3381, Vol. 76, No. 7
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.7.3374-3381.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Overexpression of the Rabies Virus Glycoprotein Results in Enhancement of Apoptosis and Antiviral Immune Response

Milosz Faber,1 Rojjanaporn Pulmanausahakul,1 Suchita S. Hodawadekar,1 Sergei Spitsin,1 James P. McGettigan,1,2 Matthias J. Schnell,2,3 and Bernhard Dietzschold1,2*

Departments of Microbiology and Immunology,1 Biochemistry and Molecular Pharmacology,3 Center for Human Virology, Thomas Jefferson University, Philadelphia, Pennsylvania 191072

Received 24 September 2001/ Accepted 26 December 2001

A recombinant rabies virus (RV) carrying two identical glycoprotein (G) genes (SPBNGA-GA) was constructed and used to determine the effect of RV G overexpression on cell viability and immunity. Immunoprecipitation analysis and flow cytometry showed that tissue culture cells infected with SPBNGA-GA produced, on average, twice as much RV G as cells infected with RV carrying only a single RV G gene (SPBNGA). The overexpression of RV G in SPBNGA-GA-infected NA cells was paralleled by a significant increase in caspase 3 activity followed by a marked decrease in mitochondrial respiration, neither of which was observed in SPBNGA-infected cells. Furthermore, fluorescence staining and confocal microscopy revealed an increased extent of apoptosis and markedly reduced neurofilament and F actin in SPBNGA-GA-infected primary neuron cultures compared with neuronal cells infected with SPBNGA, supporting the concept that RV G or motifs of the RV G gene trigger the apoptosis cascade. Mice immunized with SPBNGA-GA showed substantially higher antibody titers against the RV G and against the nucleoprotein than SPBNGA-immunized mice, suggesting that the speed or extent of apoptosis directly determines the magnitude of the antibody response.

* Corresponding author. Mailing address: Departments of Microbiology and Immunology, Thomas Jefferson University, 1020 Locust St., Philadelphia, PA 19107. Phone: (215) 503-4692. Fax: (215) 923-7145. E-mail: bdietzschold{at}reddi1.uns.tju.edu.

Journal of Virology, April 2002, p. 3374-3381, Vol. 76, No. 7
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.7.3374-3381.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Zhao, L., Toriumi, H., Kuang, Y., Chen, H., Fu, Z. F. (2009). The Roles of Chemokines in Rabies Virus Infection: Overexpression May Not Always Be Beneficial. J. Virol. 83: 11808-11818 [Abstract] [Full Text]  
  • Faber, M., Li, J., Kean, R. B., Hooper, D. C., Alugupalli, K. R., Dietzschold, B. (2009). Effective preexposure and postexposure prophylaxis of rabies with a highly attenuated recombinant rabies virus. Proc. Natl. Acad. Sci. USA 106: 11300-11305 [Abstract] [Full Text]  
  • Wirblich, C., Tan, G. S., Papaneri, A., Godlewski, P. J., Orenstein, J. M., Harty, R. N., Schnell, M. J. (2008). PPEY Motif within the Rabies Virus (RV) Matrix Protein Is Essential for Efficient Virion Release and RV Pathogenicity. J. Virol. 82: 9730-9738 [Abstract] [Full Text]  
  • Gholami, A., Kassis, R., Real, E., Delmas, O., Guadagnini, S., Larrous, F., Obach, D., Prevost, M.-C., Jacob, Y., Bourhy, H. (2008). Mitochondrial Dysfunction in Lyssavirus-Induced Apoptosis. J. Virol. 82: 4774-4784 [Abstract] [Full Text]  
  • Pulmanausahakul, R., Li, J., Schnell, M. J., Dietzschold, B. (2008). The Glycoprotein and the Matrix Protein of Rabies Virus Affect Pathogenicity by Regulating Viral Replication and Facilitating Cell-to-Cell Spread. J. Virol. 82: 2330-2338 [Abstract] [Full Text]  
  • Faber, M., Faber, M.-L., Li, J., Preuss, M. A. R., Schnell, M. J., Dietzschold, B. (2007). Dominance of a Nonpathogenic Glycoprotein Gene over a Pathogenic Glycoprotein Gene in Rabies Virus. J. Virol. 81: 7041-7047 [Abstract] [Full Text]  
  • Plesa, G., McKenna, P. M., Schnell, M. J., Eisenlohr, L. C. (2006). Immunogenicity of cytopathic and noncytopathic viral vectors.. J. Virol. 80: 6259-6266 [Abstract] [Full Text]  
  • Faber, M., Faber, M.-L., Papaneri, A., Bette, M., Weihe, E., Dietzschold, B., Schnell, M. J. (2005). A Single Amino Acid Change in Rabies Virus Glycoprotein Increases Virus Spread and Enhances Virus Pathogenicity. J. Virol. 79: 14141-14148 [Abstract] [Full Text]  
  • Wang, Z. W., Sarmento, L., Wang, Y., Li, X.-q., Dhingra, V., Tseggai, T., Jiang, B., Fu, Z. F. (2005). Attenuated Rabies Virus Activates, while Pathogenic Rabies Virus Evades, the Host Innate Immune Responses in the Central Nervous System. J. Virol. 79: 12554-12565 [Abstract] [Full Text]  
  • Kassis, R., Larrous, F., Estaquier, J., Bourhy, H. (2004). Lyssavirus Matrix Protein Induces Apoptosis by a TRAIL-Dependent Mechanism Involving Caspase-8 Activation. J. Virol. 78: 6543-6555 [Abstract] [Full Text]  
  • Prehaud, C., Lay, S., Dietzschold, B., Lafon, M. (2003). Glycoprotein of Nonpathogenic Rabies Viruses Is a Key Determinant of Human Cell Apoptosis. J. Virol. 77: 10537-10547 [Abstract] [Full Text]  
  • McGettigan, J. P., Pomerantz, R. J., Siler, C. A., McKenna, P. M., Foley, H. D., Dietzschold, B., Schnell, M. J. (2002). Second-Generation Rabies Virus-Based Vaccine Vectors Expressing Human Immunodeficiency Virus Type 1 Gag Have Greatly Reduced Pathogenicity but Are Highly Immunogenic. J. Virol. 77: 237-244 [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»