Intrahepatic induction of alpha/beta interferon eliminates viral RNA-containing capsids in hepatitis B virus transgenic mice

We have previously shown that hepatitis B virus (HBV) replication is abolis hed in the liver of HBV transgenic mice by stimuli that induce alpha/beta i nterferon (IFN-alpha/beta) in the liver. The present study was done to iden tify the step(s) in HBV replication that is affected by this cytokine in tr ansgenic mice treated with the IFN-alpha/beta inducer polyinosinic-polycyti dylic acid [poly(1-C)], Here we show that the pool of cytoplasmic HBV prege nomic RNA (pgRNA)-containing capsids is reduced 10-Fold within 9 h after po ly(1-C) administration, while there is no change in the abundance of HBV mR NA or in the translational status of cytoplasmic HBV transcripts. In additi on, we show that the pool of HBV DNA-containing capsids is not reduced to t he same degree until at least 15 h posttreatment, and we show that virus ex port is not accelerated and the half-life of virions in the serum is unchan ged. These results indicate that IFN-alpha/beta triggers intracellular even ts that either inhibit the assembly of pgRNA-containing capsids or accelera te their degradation, and that maturation and secretion of virus is respons ible for clearance of HBV capsids and their cargo of replicative intermedia tes from the cytoplasm of the hepatocyte.