Low dynamic state of viral competition in a chronic avian hepadnavirus infection

The dynamic state of infection of 11 ducks with the duck hepatitis B virus was investigated. Chronic infections were established in newly hatched duck lings by inoculation with a mixture of wild-type virus and a mutant virus w ith a partial replication defect. As expected, the wild-type virus was rapi dly enriched in the virus population during the spread of infection. Enrich ment thereafter was correlated with normal growth of the liver, with the av erage mutant-to-wild-type ratio stabilizing for at least 2 months beyond th e time at which the liver mass stabilized. Using experimentally determined growth rates for the mutant and wild-type viruses, we estimated that after the spread of infection, competition between the two virus strains was limi ted by the amount of replication required to infect new hepatocytes in the growing livers. The results suggest that, in a chronically infected liver, the selection of variants with a replication rate advantage is inefficient and that the emergence of such variants would depend on induced liver cell turnover, such as that occurring during chronic hepatitis.