1. Transfer of HBV genomes using low doses of adenovirus vectors leads to persistent infection in immune competent mice
- Author
-
Silke Arzberger, Mathias Heikenwalder, Steffi Graf, Christian Kurts, Percy A. Knolle, Yvonne A. Gäbel, Ulrike Protzer, and Li–Rung Huang
- Subjects
HBsAg ,Hepatitis B virus ,Genetic Vectors ,Dose-Response Relationship, Immunologic ,medicine.disease_cause ,Transfection ,DNA vaccination ,Viral vector ,Adenoviridae ,Hepatitis B Antigens ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Immune system ,Immunity ,medicine ,Animals ,Seroconversion ,Hepatitis B Antibodies ,030304 developmental biology ,0303 health sciences ,Hepatology ,business.industry ,Gastroenterology ,virus diseases ,Hepatitis B ,Virology ,digestive system diseases ,Immunity, Innate ,3. Good health ,HBcAg ,Immunology ,Hepatocytes ,030211 gastroenterology & hepatology ,business ,Immunocompetence ,T-Lymphocytes, Cytotoxic - 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.
- Published
- 2011