A modified murine model based on hydrodynamic injection for the analysis of chronic human hepatitis B virus infection

Abstract

Hepatitis B virus (HBV) is a persistent pathogen that causes acute and chronic necroinflammatory liver disease and is attributable to ~1 million deaths per year. In the present study, a conventional murine model was introduced based on the hydrodynamic injection of engineered replication-competent HBV DNA into the tail veins of C57BL/6 mice. In a previous study, nine in-frame ATG (start) codons in the S open reading frame (S1-S9) were analyzed. The highly conserved ATG S5 was mutated to ACG by T378C, which led to the substitution sM75T and inhibition of the production and secretion of the hepatitis B surface antigen (HBsAg), and subsequent inhibition of HBV replication. In the present study, T378C was introduced into the pAAV-HBV1.3 plasmid and was confirmed to affect HBsAg production and secretion, and HBV replication in vivo, which was in agreement with the previous in vitro results. Furthermore, the murine model was improved by co-injection of the replication-competent HBV plasmid DNA with Lipofectamine 2000 (LP). In this model, LP not only significantly enhanced HBV replication in mice, but also upregulated the expression of HBsAg and the hepatitis B core antigen. The current modified murine model was superior to the conventional murine HBV model based on HBV challenge by hydrodynamic injection.