Comparison of Antiviral Effects of Mismatched Double-Stranded RNA and 1 -(2′-Deoxy-2′,-Fluoro-β-D-Arabinofuranosyl)-5-Methyluracil (D-FMAU) against Duck Hepatitis B virus in Vitro

Abstract

The effects of mismatched double-stranded RNA (m-dsRNA) and 1-(2'-deoxy-2'-fluoro-β-D-arabinofuranosyl)-5-methyl-uracil (D-FMAU) on the replication of duck hepatitis B virus (DHBV) were examined in duck primary hepatocytes infected with DHBV. The 50% inhibitory doses of m-dsRNA and D-FMAU for the replication of DHBV DNA were 0.34±0.06 and 0.007±0.001 μg mL -1 , respectively. Mismatched dsRNA slightly inhibited the intermediate DHBV DNA at a concentration as high as 1.0 μg mL -1 , whereas the DHBV replicative form was markedly suppressed in the presence of 0.1 μg mL -1 of D-FMAU. On the other hand, m-dsRNA inhibited DHBV DNA replication even after the compound was removed from the culture medium, while the efficacy of D-FMAU did not persist after the cessation of treatment. The analysis of DHBV RNA revealed that m-dsRNA markedly inhibited DHBV RNA transcription, while D-FMAU only marginally suppressed the transcription of viral RNA. These results indicate that m-dsRNA inhibits DHBV RNA transcription rather than DHBV DNA replication and that this suppression of DHBV RNA transcription may produce persistent inhibition of DHBV replication.