This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nishino, Y. Articles by Carbone, K. M. Search for Related Content PubMed PubMed Citation Articles by Nishino, Y. Articles by Carbone, K. M.

 Previous Article  |  Next Article 

Journal of Virology, September 2002, p. 8650-8658, Vol. 76, No. 17
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.17.8650-8658.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Enhanced Neurovirulence of Borna Disease Virus Variants Associated with Nucleotide Changes in the Glycoprotein and L Polymerase Genes

Departments of Psychiatry and Behavioral Sciences,¹ Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205,⁴ Laboratory of Pediatric and Respiratory Viral Diseases, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, Maryland 20892,² Research Institute of Biosciences, Azabu University, Sagamihara 229-8501, Japan³

Received 21 February 2002/ Accepted 6 June 2002

Borna disease virus (BDV) infection produces a variety of clinical diseases, from behavioral illnesses to classical fatal encephalitis (i.e., Borna disease [BD]). Since the genomes of most BDV isolates differ by less than 5%, host factors are believed responsible for much of the reported variability in disease expression. The contribution of BDV genomic differences to variation in BD expression is largely unexplored. Here we compared the clinical outcomes of rats infected with one of two related BDV variants, CRP3 or CRNP5. Compared to rats inoculated with CRP3, adult and newborn Lewis rats inoculated with CRNP5 had more severe and rapidly fatal neurological disease, with increased damage to the hippocampal pyramidal neurons and rapid infection of brain stem neurons. To identify possible virus-specific contributions to the observed variability in disease outcome, the genomes of CRP3 and CRNP5 were sequenced. Compared to CRP3, there were four nucleotide changes in the CRNP5 variant, two each in the G protein and in the L polymerase, resulting in four amino acid changes. These results suggest that small numbers of genomic differences between BDV variants in the G protein and/or L polymerase can contribute to the variability in BD outcomes.

This article has been cited by other articles:

• Ackermann, A., Kugel, D., Schneider, U., Staeheli, P. (2007). Enhanced polymerase activity confers replication competence of Borna disease virus in mice. J. Gen. Virol. 88: 3130-3132 [Abstract] [Full Text]  
• Richter, K., Baur, K., Ackermann, A., Schneider, U., Hausmann, J., Staeheli, P. (2007). Pathogenic Potential of Borna Disease Virus Lacking the Immunodominant CD8 T-Cell Epitope. J. Virol. 81: 11187-11194 [Abstract] [Full Text]  
• Ackermann, A., Staeheli, P., Schneider, U. (2007). Adaptation of Borna Disease Virus to New Host Species Attributed to Altered Regulation of Viral Polymerase Activity. J. Virol. 81: 7933-7940 [Abstract] [Full Text]  
• Rubin, S. A., Amexis, G., Pletnikov, M., Vanderzanden, J., Mauldin, J., Sauder, C., Malik, T., Chumakov, K., Carbone, K. M. (2003). Changes in Mumps Virus Gene Sequence Associated with Variability in Neurovirulent Phenotype. J. Virol. 77: 11616-11624 [Abstract] [Full Text]