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Journal of Virology, April 2005, p. 4514-4518, Vol. 79, No. 7
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.7.4514-4518.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Mechanism of the Antiviral Action of 1-ß-D-Arabinofuranosylcytosine on Borna Disease Virus

Romain Volmer,1,2,{dagger} Jeffrey J. Bajramovic,2,{dagger} Urs Schneider,3 Sandra Ufano,4 Sylvie Pochet,5 and Daniel Gonzalez-Dunia1,2*

INSERM U563, CPTP, Toulouse,1 Unité des Virus Lents, CNRS URA 1930, Département de Virologie,2 Unité de Chimie Organique, CNRS URA 2128, Département de Biologie Structurale et Chimie, Institut Pasteur, Paris, France,5 Department of Virology, University of Freiburg, Freiburg, Germany,3 Centro Nacional de Biotecnologia (CSIC), Madrid, Spain4

Received 4 October 2004/ Accepted 19 October 2004

Borna disease virus (BDV) is a nonsegmented, negative-stranded RNA virus that causes neurological diseases in a variety of warm-blooded animal species. Recently, we showed that the nucleoside analog 1-ß-D-arabinofuranosylcytosine (Ara-C) was a potent inhibitor of BDV. This finding was surprising for an RNA virus, since Ara-C is a DNA polymerase inhibitor. Thus, we sought to better define the mechanism of action of Ara-C on BDV. Here, we show that (i) this effect is specific for an arabinoside ring carrying a cytosine base, (ii) it requires phosphorylation of the nucleotide, and (iii) it can be reversed by an excess of cytidine. Using the recently described minigenome assay for BDV, we provide evidence suggesting that Ara-C may act as a competitive inhibitor of the BDV replication complex.


* Corresponding author. Mailing address: INSERM U563, CPTP Batiment B, CHU Purpan, BP 3028, 31024 Toulouse, Cedex 3, France. Phone: 33-5-6274 4511. Fax: 33-5-6274 4558. E-mail: Daniel.Dunia{at}toulouse.inserm.fr.

{dagger} R.V. and J.J.B. contributed equally to this work.


Journal of Virology, April 2005, p. 4514-4518, Vol. 79, No. 7
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.7.4514-4518.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.