Homologous recombination between hepadnaviral genomes following in vivo DNA transfection: implications for studies of viral infectivity.

The cloned DNA of duck hepatitis B virus (DHBV) can initiate a productive infection of susceptible ducklings when presented by direct intrahepatic injection. We have examined the effects of the structure of the incoming DNA upon the outcome of this in vivo transfection. Plasmid-linked DHBV genomes of greater than unit length regularly give rise to infectious virus irrespective of the location of the plasmid insert on the transcriptional map. When mutant DHBV genomes are coinjected with subgenomic viral DNA fragments spanning the mutation, wild-type recombinants arise. These results indicate that, as in transfection of cultured cells, in vivo transfection of hepatocytes is regularly followed by homologous recombination involving incoming DNA molecules. These frequent recombination events will complicate efforts to use in vivo transfection for certain genetic analyses of hepadnaviruses.