Detection of HBV RNA in Serum of Patients

Cell-free RNA of a different origin is known to circulate in the blood (1 –3 ). This finding has also been reported for RNA specified by viruses with a DNA genome, such as the hepatitis B virus (HBV)(4 ). In the infected cell, genomic and subgenomic HBV-RNA molecules are synthesized from episomal genomes. Within virions, only the (−) strands of the genomes (3.2 kb) are complete, whereas the (+) strands are incomplete. The genomes replicate via the reverse transcription of genomic RNA intermediates. These pregenomes are packaged into nucleocapsids and degraded during the synthesis of the DNA (−) strand (5 ). Upon completion of (−) strand DNA synthesis, the capsids mature into the enveloped virions (Dane particles), which are found in the sera of infected individuals (6 ). Subgenomic viral transcript RNAs do exist but are not packaged into nucleocapsids (5 ). Based on these observations, there should be no replication-related release of HBV-RNA from hepatocytes into the blood. However, damage to liver cells may discharge viral RNA contained in nucleocapsids or as free forms.