FIG. 2.

Time course and dose response of HBV inhibition. (A) Groups of age-, sex-, and serum HBeAg-matched transgenic mice (3 mice per group) were injected intravenously with a single dose of 1 mg/kg bortezomib and were then analyzed 1, 2, 3, or 6 days postinjection. (B) Groups of age-, sex-, and serum HBeAg-matched transgenic mice (3 to 4 mice per group) were injected intravenously with a single dose of 0.2 mg/kg, 1 mg/kg, or 5 mg/kg bortezomib and were then analyzed 24 h postinjection. HBV replication in the liver was measured by Southern blot (SB) analysis of relaxed-circle (RC) and single-stranded (SS) DNA replication forms and was compared to levels in control animals that did not receive the drug. The expression of 3.5- and 2.1-kb HBV mRNA from total liver RNA was examined by Northern blot (NB) analysis and was compared to the expression of the GAPDH housekeeping gene. HBcAg levels were measured by Western blot (WB) analysis and were compared to β-actin expression. The level of serum alanine aminotransferase (sALT) was determined in order to assess hepatocellular toxicity.