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 site-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 about one-half that of wild-type virus. Accordingly, wild-type virus was rapidly selected during the spread of infection. During the chronic phase of the infection, however, two selection patterns were seen. In 4 of 10 ducks, the wild-type virus slowly replaced the precore mutant. In another four ducks, the precore mutant virus slowly replaced the wild-type virus. In the remaining two ducklings, ratios of wild-type and precore mutant virus fluctuated, 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 their original replication defect. Replacement of wild-type virus, however, correlated with elevated anti-core antibody titers, which continued to increase with time. The selection of a precore-negative strain of DHBV may be analogous to the selection for precore mutants of HBV during chronic hepatitis in humans.
Zhang
Y Y
YY
Department of Molecular Genetics and Microbiology, The University of New Mexico School of Medicine, Albuquerque, New Mexico 87131, USA.
Summers
J
J
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D002908:Chronic Disease; D004372:Ducks; D005838:Genotype; D018347:Hepadnaviridae Infections / Q000276:immunology / Q000821:virology*; D015611:Hepatitis B Virus, Duck / Q000235:genetics* / Q000276:immunology / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D014779:Virus Replication
D000914:Antibodies, Viral