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Journal of Virology, June 2002, p. 6268-6276, Vol. 76, No. 12
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.12.6268-6286.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

1-ß-D-Arabinofuranosylcytosine Inhibits Borna Disease Virus Replication and Spread

Jeffrey J. Bajramovic,1 Sylvie Syan,1 Michel Brahic,1 Juan Carlos de la Torre,2 and Daniel Gonzalez-Dunia1*

Unité des Virus Lents, CNRS URA 1930, Institut Pasteur, Paris, France,1 Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 920372

Received 13 December 2001/ Accepted 22 March 2002

Borna disease virus (BDV) is a nonsegmented, negative-strand RNA virus that causes neurological diseases in a variety of warm-blooded animal species. There is general consensus that BDV can also infect humans, being a possible zoonosis. Although the clinical consequences of human BDV infection are still controversial, experimental BDV infection is a well-described model for human neuropsychiatric diseases. To date, there is no effective treatment against BDV. In this paper, we demonstrate that the nucleoside analog 1-ß-D-arabinofuranosylcytosine (Ara-C), a known inhibitor of DNA polymerases, inhibits BDV replication. Ara-C treatment inhibited BDV RNA and protein synthesis and prevented BDV cell-to-cell spread in vitro. Replication of other negative-strand RNA viruses such as influenza virus or measles virus was not inhibited by Ara-C, underscoring the particularity of the replication machinery of BDV. Strikingly, Ara-C treatment induced nuclear retention of viral ribonucleoparticles. These findings could not be attributed to known effects of Ara-C on the host cell, suggesting that Ara-C directly inhibits the BDV polymerase. Finally, we show that Ara-C inhibits BDV replication in vivo in the brain of infected rats, preventing persistent infection of the central nervous system as well as the development of clinical disease. These findings open the way to the development of effective antiviral therapy against BDV.

* Corresponding author. Mailing address: Unité des Virus Lents, CNRS URA 1930, Institut Pasteur, 25-28 Rue du Docteur Roux, 75724 Paris, France. Phone: 33-1-4568 8771. Fax: 33-1-4061 3167. E-mail: ddune{at}pasteur.fr.

Journal of Virology, June 2002, p. 6268-6276, Vol. 76, No. 12
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.12.6268-6286.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Volmer, R., Bajramovic, J. J., Schneider, U., Ufano, S., Pochet, S., Gonzalez-Dunia, D. (2005). Mechanism of the Antiviral Action of 1-{beta}-D-Arabinofuranosylcytosine on Borna Disease Virus. J. Virol. 79: 4514-4518 [Abstract] [Full Text]  
  • Bajramovic, J. J., Volmer, R., Syan, S., Pochet, S., Gonzalez-Dunia, D. (2004). 2'-Fluoro-2'-Deoxycytidine Inhibits Borna Disease Virus Replication and Spread. Antimicrob. Agents Chemother. 48: 1422-1425 [Abstract] [Full Text]  
  • Bajramovic, J. J., Munter, S., Syan, S., Nehrbass, U., Brahic, M., Gonzalez-Dunia, D. (2003). Borna Disease Virus Glycoprotein Is Required for Viral Dissemination in Neurons. J. Virol. 77: 12222-12231 [Abstract] [Full Text]  


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