We are interested in developing a small animal model to study pathogenesis of HAV. To do so, we produced transgenic mice carrying the hepatitis A virus cellular receptor-1 (havcr-1). Inoculation of HAV grown in cell lines of monkey origin into the liver of havcr-1 transgenic and nontransgenic mice resulted in the production of anti-HAV antibodies. Since antibody production cleared the virus without apparent signs of disease, we decided to adapt HAV to grow in a mouse liver cell line transfected with the cDNA coding for havcr-1. We hypothesized that a virus adapted to grow in mouse liver cells would replicate faster in the liver and have a better chance of causing disease. The results of this experiment are currently being evaluated.
