The role of inducible nitric oxide synthase in a murine acute hepatitis B virus (HBV) infection model induced by hydrodynamics-based in vivo transfection of HBV-DNA

Background/Aims: Inducible nitric oxide synthase (iNOS) is found to have antiviral activity. Its role is evaluated using a murine acute hepatitis B virus (HBV) infection model. Methods: pHBV3.6 plasmid containing HBV genome was injected into mice by hydrodynamics-based in vivo transfection. HBV antigenemia and serum HBV-DNA were detected by enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction, respectively. HBV replication in liver was analyzed by Northern and Southern blot. Intrahepatic leukocytes were isolated and analyzed with flow cytometry. Results: After hydrodynamics injection of pHBV3.6, HBV genome was synthesized in the liver and HBV-DNA, as well as hepatitis B surface antigen and hepatitis B e antigen were secreted into the blood. Anti-HBV antibody responses developed afterward. A murine acute HBV infection model was established with hydrodynamics injection of non-transponase based HBV-DNA. Using this protocol in iNOS deficient or wild type B6 mice, the level of HBV transcript, replicative intermediate, and antigenemia were higher in iNOS(-/-) than in B6 mice. The intrahepatic leukocytes in iNOS(-/-) mice were also affected after transfection. Conclusions: Our data suggests that the iNOS expression not only affects the HBV clearance, but also modulates the infiltrating leukocytes response to HBV antigens. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.