Transgenic mice expressing hepatitis B virus as a model for drug evaluation

摘要

Transgenic mice that constitutively express Hepatitis B Virus were used as a whole-animal model system to evaluate antiviral drugs and cytokines for the potential to reduce HBV DNA titers in the liver and serum. Lamivudine was shown to decrease HBV replicative intermediates in both the liver and serum, as shown through Southern blot analysis and quantitative serum polymerase chain reaction (PCR) assay. Another compound, ST55526, was not effective in reducing HBV DNA titers in the liver, but was effective in reducing titers in the serum. Two other drugs were ineffective in reducing HBV titers in either the liver or serum. Interferon alpha (B/D) was not effective in reducing viral titers in ovarectomized female transgenic mice.;A quantitative serum PCR assay was developed that used a calibrated internal control plasmid. Using this internal control facilitated the accurate calculation of unknown amounts of HBV DNA in serum samples using of densitometic analysis of bands resolved by electrophoresis.