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Antimicrobial Agents and Chemotherapy, May 2008, p. 1820-1828, Vol. 52, No. 5
0066-4804/08/$08.00+0     doi:10.1128/AAC.01181-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Iminosugars in Combination with Interferon and Ribavirin Permanently Eradicate Noncytopathic Bovine Viral Diarrhea Virus from Persistently Infected Cells ^,

Oxford Glycobiology Institute, Department of Biochemistry, South Parks Road, Oxford OX1 3QU, United Kingdom,¹ Institute of Biochemistry, Splaiul Independentei, 296, Sector 6, Bucharest 77700, Romania²

Received 7 September 2007/ Returned for modification 16 October 2007/ Accepted 25 February 2008

We evaluated interferon (IFN) and ribavirin (RBV) as dual therapy and as part of triple-combination therapies with the iminosugars N-butyl-deoxynojirimycin (NB-DNJ), N-nonyl-deoxynojirimycin, and N-7-oxanonyl-6-deoxymethyl-galactonojirimycin. The ability of these compounds to clear bovine viral diarrhea virus (BVDV), a surrogate model for hepatitis C virus (HCV), from a persistently infected Madin-Darby bovine kidney cells cell line was determined by monitoring the secretion of viral RNA and the infectivity of secreted virions. In the BVDV system, after treatment with IFN-RBV alone, viral rebound was observed immediately after removal of the drugs. In contrast, we demonstrate that a triple drug combination of IFN, RBV, and an iminosugar eradicated the BVDV infection in a time- and a dose-dependent manner, leading to sustained viral clearance. Importantly, in the case of NB-DNJ, the sustained viral clearance was achieved by using physiologically relevant and tolerated drug concentrations. Therefore, the use of a triple-combination therapy that includes an iminosugar may prove to be of greater therapeutic value for the treatment of HCV infection than the use of IFN-RBV alone.

Published ahead of print on 3 March 2008.

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