Rapid resolution of duck hepatitis B virus infections occurs after massive hepatocellular involvement

Abstract

A study was carried out to determine some of the factors that might distinguish transient from chronic hepadnavirus infection. First, to better characterize chronic infection, Pekin ducks, congenitally infected with the duck hepatitis B virus (DHBV), were used to assess age-dependent variations in viremia, percentage of DHBV-infected hepatocytes, and average levels of DNA replication intermediates in the cytoplasm and of covalently closed circular DNA in the nuclei of infected hepatocytes. Levels of viremia and viral DNA were found to peak at about the time of hatching but persisted at relatively constant levels in chronically infected birds up to 2 years of age. The percentage of infected hepatocytes was also constant, with DHBV replication in virtually 100% of hepatocytes in all birds. Next, we found that adolescent ducks inoculated intravenously with a large dose of DHBV also developed massive infection of hepatocytes with an early but low-level viremia, followed by rapid development of a neutralizing antibody response. No obvious quantitative or qualitative differences between transiently and chronically infected liver tissue were detected in the intracellular markers of viral replication examined. However, in the adolescent duck experiment, DHBV infection was rapidly cleared from the liver even when up to 80% of hepatocytes were initially infected. In all of these ducks, clearance of infection was accompanied by only a mild hepatitis, with no evidence that massive cell death contributed to the clearance. This finding suggested that mechanisms in addition to immune-mediated destruction of hepatocytes might make major contributions to clearance of infections, including physiological turnover of hepatocytes in the presence of a neutralizing antibody response and/or spontaneous loss of the capacity of hepatocytes to support virus replication.

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

“…However, even high m.o.i. hepadnavirus infections in adult ducks 25 and woodchucks 26 resolve rapidly, i.e., as when virtually every hepatocyte is infected initially with very high doses of virus inoculum. 25,26 Moreover, as stated earlier, chronicity as an outcome was never absolute among neonatally infected woodchucks.…”

“…hepadnavirus infections in adult ducks 25 and woodchucks 26 resolve rapidly, i.e., as when virtually every hepatocyte is infected initially with very high doses of virus inoculum. 25,26 Moreover, as stated earlier, chronicity as an outcome was never absolute among neonatally infected woodchucks. Perhaps the precise timing of key maturational events in the liver varies from animal-to-animal during neonatal growth (and/or regeneration), and thereby contributes to the observed partitioning of chronic and resolved infections within a defined age group.…”

Recent advancements for the evaluation of anti-viral activities of natural products

“…Human HBV-transgenic mice (5 weeks old with positive plasma HBsAg) from lineage 1.3.32 [96] and maintained under a 12/12 h light/dark cycle with a standard commercial diet and water ad libitum. Ducklings at one day of age were intravenously infected with a 5.7 Â 10 6 viral genome equivalent (VGE, 1 VGE = 3.3 Â 10 6 pg) of DHBV [97]. Seven days later, extract, solubilised in isotonic saline solution, was administered (112, 56, 28 mg/kg) once daily orally in a liquid diet for 10 days.…”

Repopulation of mouse liver with human hepatocytes and in vivo infection with hepatitis B virus

“…Animal models based on HBV-related hepadnaviruses, such as woodchuck and Pekin duck hepatitis B viruses, are often used for assessment of antiviral drugs [6][7][8] and have provided important information about factors involved in establishment of virus infection, viral persistence, and hepatocarcinogenesis. [9][10][11][12][13][14] However, woodchucks are relatively large animals of outbred origins that are difficult to handle in many laboratories, and chronic hepadnavirus infection in birds does not lead to cancer. The development of HBV-expressing transgenic mice has also provided important insights regarding viral pathobiology and the role of HBV gene products in hepatocellular injury.…”