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 Ackermann, A.
Right arrow Articles by Schneider, U.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ackermann, A.
Right arrow Articles by Schneider, U.

 Previous Article  |  Next Article 

Journal of Virology, August 2007, p. 7933-7940, Vol. 81, No. 15
0022-538X/07/$08.00+0     doi:10.1128/JVI.00334-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Adaptation of Borna Disease Virus to New Host Species Attributed to Altered Regulation of Viral Polymerase Activity{triangledown}

Andreas Ackermann, Peter Staeheli,* and Urs Schneider*

Department of Virology, University of Freiburg, D-79104 Freiburg, Germany

Received 15 February 2007/ Accepted 14 May 2007

Borna disease virus (BDV) can persistently infect the central nervous system of a broad range of mammalian species. Mice are resistant to infections with primary BDV isolates, but certain laboratory strains can be adapted to replicate in mice. We determined the molecular basis of adaptation by studying mutations acquired by a cDNA-derived BDV strain during one brain passage in rats and three passages in mice. The adapted virus propagated efficiently in mouse brains and induced neurological disease. Its genome contained seven point mutations, three of which caused amino acid changes in the L polymerase (L1116R and N1398D) and in the polymerase cofactor P (R66K). Recombinant BDV carrying these mutations either alone or in combination all showed enhanced multiplication speed in Vero cells, indicating improved intrinsic viral polymerase activity rather than adaptation to a mouse-specific factor. Mutations R66K and L1116R, but not N1398D, conferred replication competence of recombinant BDV in mice if introduced individually. Virus propagation in mouse brains was substantially enhanced if both L mutations were present simultaneously, but infection remained mostly nonsymptomatic. Only if all three amino acid substitutions were combined did BDV replicate vigorously and induce early disease in mice. Interestingly, the virulence-enhancing effect of the R66K mutation in P could be attributed to reduced negative regulation of polymerase activity by the viral X protein. Our data demonstrate that BDV replication competence in mice is mediated by the polymerase complex rather than the viral envelope and suggest that altered regulation of viral gene expression can favor adaptation to new host species.

* Corresponding author. Mailing address: Department of Virology, University of Freiburg, Hermann-Herder-Straße 11, D-79104 Freiburg, Germany. Phone for Urs Schneider: 49-761-203-6622. Fax: 49-761-203-5350. E-mail: urs.schneider{at}uniklinik-freiburg.de. Phone for Peter Staeheli: 49-761-203-6579. Fax: 49-761-203-5350. E-mail: peter.staeheli{at}uniklinik-freiburg.de

{triangledown} Published ahead of print on 23 May 2007.

Journal of Virology, August 2007, p. 7933-7940, Vol. 81, No. 15
0022-538X/07/$08.00+0     doi:10.1128/JVI.00334-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Poenisch, M., Burger, N., Staeheli, P., Bauer, G., Schneider, U. (2009). Protein X of Borna Disease Virus Inhibits Apoptosis and Promotes Viral Persistence in the Central Nervous Systems of Newborn-Infected Rats. J. Virol. 83: 4297-4307 [Abstract] [Full Text]  
  • 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]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»