Enrichment of a precore-minus mutant of duck hepatitis B virus in experimental mixed infections

A precore-deficient mutant of duck hepatitis B virus (DHBV) produced by sit e directed mutagenesis was tested for its ability to compete with wild-type virus in a mixed infection of 3-day-old ducklings, The mutation was shown to produce a cis-acting defect, resulting in a replication rate that was ab out one-half that of wild-type virus. Accordingly, wild-type virus was rapi dly selected during the spread of infection. During the chronic phase of th e infection, however, two selection patterns Here seen. In 4 of 10 ducks, t he wild-type virus slowly replaced the precore mutant. In another four duck s, the precore mutant virus slowly replaced the wild-type virus. In the rem aining two ducklings, ratios of wild-type and precore mutant virus fluctuat ed, with wild-type virus slowly predominating, The replacement of wild type virus was not due to the emergence of a rapidly replicating variant of the precore mutant, since genomes cloned from the infected ducks retained thei r original replication defect. Replacement of wild-type virus, however, cor related with elevated anti-core antibody titers, which continued to increas e with time. The selection of a precore-negative strain of DHBV may be anal ogous to the selection for precore mutants of HBV during chronic hepatitis in humans.