Mechanism of the antiviral action of 1-beta-D-arabinofuranosylcytosine on Borna disease virus.
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-beta-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.
Volmer
Romain
R
INSERM U563, CPTP, Toulouse, France.
Bajramovic
Jeffrey J
JJ
Schneider
Urs
U
Ufano
Sandra
S
Pochet
Sylvie
S
Gonzalez-Dunia
Daniel
D
D000998:Antiviral Agents / Q000494:pharmacology*; D001891:Borna disease virus / Q000187:drug effects* / Q000502:physiology; D003561:Cytarabine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D003561:Cytarabine