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 Schnell, M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Faber, M.
Right arrow Articles by Schnell, M. J.

 Previous Article  |  Next Article 

Journal of Virology, November 2005, p. 14141-14148, Vol. 79, No. 22
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.22.14141-14148.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

A Single Amino Acid Change in Rabies Virus Glycoprotein Increases Virus Spread and Enhances Virus Pathogenicity

Milosz Faber,1 Marie-Luise Faber,2 Amy Papaneri,1 Michael Bette,3 Eberhard Weihe,3 Bernhard Dietzschold,1 and Matthias J. Schnell1*

Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107,1 Molecular Targeting Technologies, 882 S. Matlack St., Suite 105, West Chester, Pennsylvania 19382,2 Department of Molecular Neuroscience, Institute of Anatomy and Cell Biology, Philipps University Marburg, Marburg, Germany3

Received 16 June 2005/ Accepted 29 August 2005

Several rabies virus (RV) vaccine strains containing an aspartic acid (Asp) or glutamic acid (Glu) instead of an arginine (Arg) at position 333 of the RV glycoprotein (G) are apathogenic for immunocompetent mice even after intracranial inoculation. However, we previously showed that the nonpathogenic phenotype of the highly attenuated RV strain SPBNGA, which contains a Glu at position 333 of G, is unstable when this virus is passaged in newborn mice. While the Glu333 remained unchanged after five mouse passages, an Asn194->Lys194 mutation occurred in RV G. This mutation was associated with increased pathogenicity for adult mice. Using site-directed mutagenesis to exchange Asn194 with Lys194 in the G protein of SPBNGA, resulting in SPBNGA-K, we show here that this mutation is solely responsible for the increase in pathogenicity and that the Asn194->Lys194 mutation does not arise when Asn194 is exchanged with Ser194 (SPBNGA-S). Our data presented indicate that the increased pathogenicity of SPBNGA-K is due to increased viral spread in vivo and in vitro, faster internalization of the pathogenic virus into cells, and a shift in the pH threshold for membrane fusion. These results are consistent with the notion that the RV G protein is a major contributor to RV pathogenesis and that the more pathogenic RVs escape the host responses by a faster spread than that of less pathogenic RVs.

* Corresponding author. Mailing address: 233 South 10th Street, Suite 350 BLSB, Philadelphia, PA 19107-5541. Phone: (215) 503-4634. Fax: (215) 503-5393. E-mail: matthias.schnell{at}jefferson.edu.

Journal of Virology, November 2005, p. 14141-14148, Vol. 79, No. 22
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.22.14141-14148.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • 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]  
  • Fehlner-Gardiner, C., Nadin-Davis, S., Armstrong, J., Muldoon, F., Bachmann, P., Wandeler, A. (2008). ERA VACCINE-DERIVED CASES OF RABIES IN WILDLIFE AND DOMESTIC ANIMALS IN ONTARIO, CANADA, 1989-2004. J Wildl Dis 44: 71-85 [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]  
  • Blanton, J. D., Meadows, A., Murphy, S. M., Manangan, J., Hanlon, C. A., Faber, M.-L., Dietzschold, B., Rupprecht, C. E. (2006). Vaccination of Small Asian Mongoose (Herpestes javanicus) Against Rabies.. J Wildl Dis 42: 663-666 [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»