Transfer of HBV Genomes Using Low Doses of Adenovirus Vectors Leads to Persistent Infection in Immune Competent Mice

Gastroenterology. 2012 Jun;142(7):1447-50.e3. doi: 10.1053/j.gastro.2012.03.006. Epub 2012 Mar 14.

Abstract

Studies of mechanisms responsible for the persistence of hepatitis B virus (HBV) infection have been hindered by a lack of appropriate animal models. HBV genomes can be delivered to livers of mice using hydrodynamic injection or high doses of an adenoviral vector; these lead to clearance of HBV. We found that infection of immunocompetent mice with low doses of an adenoviral vector resulted in persistent HBV infection; the mice neither underwent seroconversion to production of antibodies against HBV nor developed a strong HBV-specific effector T-cell response. As in patients with chronic HBV infection, DNA vaccination failed to generate T cells that cleared infection. This model of persistent HBV infection could be used to study the pathogenesis of chronic HBV infection and develop new therapeutic strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae*
  • Animals
  • Dose-Response Relationship, Immunologic
  • Genetic Vectors*
  • Hepatitis B / immunology*
  • Hepatitis B Antibodies / biosynthesis
  • Hepatitis B Antigens / analysis
  • Hepatitis B virus / genetics*
  • Hepatocytes / immunology
  • Hepatocytes / virology
  • Immunity, Innate
  • Immunocompetence
  • Mice
  • T-Lymphocytes, Cytotoxic / immunology
  • Transfection

Substances

  • Hepatitis B Antibodies
  • Hepatitis B Antigens