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Journal of Virology, May 2005, p. 5819-5832, Vol. 79, No. 9
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.9.5819-5832.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Effect of Antiviral Treatment with Entecavir on Age- and Dose-Related Outcomes of Duck Hepatitis B Virus Infection

Wendy K. Foster,1 Darren S. Miller,1 Catherine A. Scougall,1 Ieva Kotlarski,2 Richard J. Colonno,3 and Allison R. Jilbert1,2*

School of Molecular and Biomedical Science, University of Adelaide, North Terrace, Adelaide SA 5005, Australia,1 Infectious Diseases Laboratories, Institute of Medical and Veterinary Science, Frome Road, Adelaide SA 5000, Australia,2 Bristol-Myers Squibb Pharmaceutical Research Institute, Research Parkway, Wallingford, Connecticut 064923

Received 13 September 2004/ Accepted 17 December 2004

Entecavir (ETV), a potent inhibitor of the hepadnaviral polymerases, prevented the development of persistent infection when administered in the early stages of duck hepatitis B virus (DHBV) infection. In a preliminary experiment, ETV treatment commenced 24 h before infection showed no significant advantage over simultaneous ETV treatment and infection. In two further experiments 14-day-old ducks were inoculated with DHBV-positive serum containing 104, 106, 108, or 5 x 108 viral genomes (vge) and were treated orally with 1.0 mg/kg of body weight/day of ETV for 14 or 49 days. A relationship between virus dose and infection outcome was seen: non-ETV-treated ducks inoculated with 104 vge had transient infection, while ducks inoculated with higher doses developed persistent infection. ETV treatment for 49 days did not prevent initial infection of the liver but restricted the spread of infection more than ~1,000-fold, a difference which persisted throughout treatment and for up to 49 days after withdrawal. Ultimately, three of seven ETV-treated ducks resolved their DHBV infection, while the remaining ducks developed viremia and persistent infection after a lag period of at least 63 days. ETV treatment for 14 days also restricted the spread of infection, leading to marked and sustained reductions in the number of DHBV-positive hepatocytes in 7 out of 10 ducks. In conclusion, short-term suppression with ETV provides opportunity for the immune response to successfully control DHBV infection. Since DHBV infection of ducks provides a good model system for HBV infection in humans, it seems likely that ETV may be useful in postexposure therapy for HBV infection aimed at preventing the development of persistent infection.

* Corresponding author. Mailing address: Hepatitis Virus Research Laboratory, Infectious Diseases Laboratories, Institute of Medical and Veterinary Science, Frome Rd., Box 14 Rundle Mall, Adelaide, SA 5000, Australia. Phone: 61-8-8303 5399. Fax: 61-8-8303 7532. E-mail: allison.jilbert{at}adelaide.edu.au.

Journal of Virology, May 2005, p. 5819-5832, Vol. 79, No. 9
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.9.5819-5832.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





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