Portal de Periódicos da CAPES

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

2008; American Society for Microbiology; Volume: 52; Issue: 5 Linguagem: Inglês

10.1128/aac.01181-07

1098-6596

Stephen D. Woodhouse, Caroline Smith, Maud Michelet, Norica Branza‐Nichita, Mark S. Hussey, Raymond A. Dwek, Nicole Zitzmann,

Virus-based gene therapy research

ABSTRACT We evaluated interferon (IFN) and ribavirin (RBV) as dual therapy and as part of triple-combination therapies with the iminosugars N -butyl-deoxynojirimycin ( N B-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 N B-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.