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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.



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