Characterization of Age- and Dose-Related Outcomes of Duck Hepatitis B Virus Infection

Abstract

Experimental inoculation of naive ducks with duck hepatitis B virus (DHBV) can lead to one of three outcomes, namely, persistent viremia, transient infection with or without viremia, or no evidence of infection. The ability of individual ducks to resolve DHBV infection was found to be linked to the age of the duck at the time of inoculation and the dose of inoculated virus. (1) In recently hatched ducks inoculated intravenously (i.v.) with 4 x 10(4) DHBV DNA genomes, a switch from persistent viremia to transient antibody appearance was seen at an age of inoculation between 7 and 14 days. A 25-fold increase in the dose of virus (1 x 10(6) DHBV genomes) delayed this switch by 7 days. (2) When 4-month-old ducks were inoculated i.v. with different doses of virus, only those receiving the highest dose (2 x 10(11) DHBV genomes) showed viremia and extensive viral replication and histological changes in the liver; 2/3 ducks in this group had a transient infection, while the third duck had viral replication and histological changes in the liver that were still present at day 120 postinoculation (p.i.). In all ducks receiving lower doses (1 x 10(3), 1 x 10(6), 1 x 10(9) DHBV genomes) antibodies to viral surface and core antigens developed without detectable viral replication in the liver on days 6, 9, or 12 p.i. (3) When 10- to 16-month-old ducks were inoculated i.v. with 2 x 10(11) DHBV genomes, all showed extensive viral replication in hepatocytes and mild to moderate histological changes in the liver on days 4 or 6 p.i. In 4/5 ducks viremia was not detected, anti-surface antibodies were first detected on day 8 p.i., and viral DNA and antigen were cleared from the liver by days 35-47 p.i. The remaining duck became viremic with persistence of virus in the liver until at least day 46 p.i. The findings of the study are consistent with a model for noncytopathic viruses (R. M. Zinkernagel (1996) Science 271, 173-178).

Effects of age and viral determinants on chronicity as an outcome of experimental woodchuck hepatitis virus infection

“…Such processes appear to change relatively soon after birth in that the susceptibility to chronicity as an outcome diminishes substantially sometime between the second and eighth week of age. This change-over in susceptibility to chronicity appears more gradual than in the duck 24 and is perhaps more representative of the decreasing, age-specific risk for chronic outcome evident in human HBV infection. 18 Host factors other than immunological status could also influence the chronicity rate in hepadnavirus infection, but the available evidence is less convincing.…”

“…Although the measurable infectious titers of WHV were as high or higher than those of some HBV 3,23 and duck HBV (DHBV) 24 inocula, results for IV titrations of HBV in chimps 23 and of DHBV in ducks 24 indicate that 1 infectious dose 50% of virus corresponded to between 1 and 10 GEq. In 1 IV titration experiment in adult woodchucks, the relative infectivity of WHV8P0 was P/I ϭ 179.…”

“…The infectious dose of DHBV influences incubation time in the duck model and also influences the early time window within which young ducklings are susceptible to chronicity as an outcome of infection. 24 The infectious dose of WHV clearly affected chronicity rates in the neonatal woodchuck model, but further interpretations are possible. For example, virus dose affected the time to seroconversion in the case of WHV7P1 (Table 4), thus inducing a potential age effect on outcome during a critical time in development.…”

“…This differs from the duck model of DHBV infection. 24 In the duck, there is a switch from essentially 100% chronic outcome to 100% resolved outcome after inoculations at 14 and 21 days of age, respectively, when using 1 ϫ 10 6 DHBV GEq (P/I ϭ approximately 1). The switch point occurred between 7 and 14 days of age at lower doses of DHBV.…”

“…The switch point occurred between 7 and 14 days of age at lower doses of DHBV. 24 Host factors clearly affect the chronicity rate in WHV infection, as shown when the same strain and dose of WHV were administered to woodchucks of different ages. The ability to resolve infections with WHV7P1 was clearly improved with increasing age at inoculation.…”