Mechanism Of Hepadnavirus Persistence In The Hydrodynamic Injection Mouse Model

Background and aims:Both viral and host factors may contribute to the persistence of hepatitis B virus (HBV). In the mouse model, the HBV-related virus, woodchuck hepatitis virus (WHV), was able to persistently replicate after hydrodynamic injection while HBV was usually cleared. We generated HBV and WHV chimeras to determine the WHV genome region responsible for persistence.Methods:HBV genome regions were replaced by the corresponding WHV genome regions and cloned as1.3-fold overlength genome. The HBV-WHV chimeric genomes were hydrodynamically injected into BALB/c mice. The replication of chimeric genomes in mice was examined.Results:Seven chimeric genomes were constructed and were found to be able to express surface and nucleocapsid proteins in vitro and in vivo. The replication in mice was confirmed by detection of viral surface protein and viral DNA. The HBV-WHV chimeric genomes containing the part of WHV core region were able to persist. The presence of this WHV genome region was associated with low levels of viral DNA, indicating a reduced replication activity.Conclusion:These results are consistent with findings in other studies that the hepadnaviral nucleocapsid protein is an important determinant for viral persistence vs. clearance.