scholarly journals The guanine nucleoside analog penciclovir is active against chronic duck hepatitis B virus infection in vivo.

1996 ◽  
Vol 40 (2) ◽  
pp. 413-418 ◽  
Author(s):  
E Lin ◽  
C Luscombe ◽  
Y Y Wang ◽  
T Shaw ◽  
S Locarnini
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Nucleoside Analog ◽  
Genome Replication ◽  
Viral Dna ◽  
Duck Hepatitis B Virus ◽  
Protein Levels ◽  
Duck Hepatitis ◽  
B Virus

Ducks congenitally infected with duck hepatitis B virus (HBV) were treated with the antiviral guanine nucleoside analog penciclovir for 4 weeks at a dose of 10 mg/kg of body weight per day. The effects of treatment on viremia and intrahepatic viral genome replication, transcription, and translation were examined. In seven of eight penciclovir-treated ducks, viremia was barely detectable after a week of treatment. After 4 weeks of treatment, molecular hybridization studies showed that intrahepatic viral DNA, RNA, and protein levels were significantly reduced compared with those in placebo-treated controls. Synthesis of all viral replicative intermediates, including the normally persistent viral supercoiled DNA species, was inhibited by penciclovir treatment. Examination of liver tissue sections after in situ DNA hybridization or immunohistochemical staining confirmed that viral DNA and protein synthesis had been profoundly inhibited in most hepatic parenchymal cells. However, small subpopulations of cells, in particular the small bile duct epithelial cells, remained strongly positive for duck HBV antigens and DNA despite treatment. There was no evidence of toxicity associated with penciclovir therapy. This study confirms the safety and potent antihepadnaviral activity of penciclovir in vivo but indicates that further improvements in antiviral therapy will be required to completely eliminate HBV infection.

scholarly journals Long-Term Therapy with the Guanine Nucleoside Analog Penciclovir Controls Chronic Duck Hepatitis B Virus Infection In Vivo

1998 ◽  
Vol 42 (8) ◽  
pp. 2132-2137 ◽  
Author(s):  
Enjarn Lin ◽  
Carolyn Luscombe ◽  
Danni Colledge ◽  
Yan Yan Wang ◽  
Stephen Locarnini
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Nucleoside Analog ◽  
Term Therapy ◽  
Duck Hepatitis B Virus ◽  
Protein Levels ◽  
Duck Hepatitis ◽  
B Virus

ABSTRACT Ducks congenitally infected with duck hepatitis B virus (DHBV) were treated with the antiviral guanine nucleoside analog penciclovir for 12 or 24 weeks at a dosage of 10 mg/kg of body weight per day. By the completion of both 12 and 24 weeks of therapy, molecular hybridization studies of the liver tissue revealed that the viral DNA, RNA, and protein levels were significantly reduced compared to those in the placebo-treated controls. Penciclovir treatment for 12 or 24 weeks was not associated with any toxicity, establishing the efficacy and safety of long-term penciclovir therapy in chronic DHBV infection.

scholarly journals Kinetics of early molecular events in duck hepatitis B virus replication in primary duck hepatocytes

1999 ◽  
Vol 80 (8) ◽  
pp. 2127-2135 ◽  
Author(s):  
M. Qiao ◽  
C. A. Scougall ◽  
A. Duszynski ◽  
C. J. Burrell
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Nuclear Membrane ◽  
Post Inoculation ◽  
Viral Dna ◽  
Duck Hepatitis B Virus ◽  
Duck Hepatitis ◽  
B Virus ◽  
Kinetics Of

This paper describes the use of one-step growth conditions to study the kinetics of duck hepatitis B virus (DHBV) replication in primary duck hepatocytes. Synchronized infection was achieved using partially purified DHBV virions at an m.o.i. of 640 DHBV DNA-containing virions per cell, and these conditions were shown to produce a single cycle of infection. In this model, input purified DHBV DNA was rapidly internalized by cells at ⩾0·5 h, and localized to the nucleus by 4 h, but both covalently closed circular (CCC) DNA and single-stranded DNA were not detected until 48 h post-inoculation (p.i.), suggesting that there was a ⩾40 h delay between DHBV localization to the nucleus and formation of CCC DNA. In contrast, CCC DNA can be first detected in hepatocytes at 6 h p.i. in in vivo infection of ducks with the same DHBV strain. In an analysis of the nuclear transport of the DHBV genome, release of nuclear viral DNA from a particulate form to a soluble nucleoplasmic form was only 50% complete by 48 h p.i. However, this process occurred simultaneously with genome uncoating since all soluble nucleoplasmic DHBV DNA was free of nucleocapsid material; this suggests that nucleocapsid disassembly and genome uncoating may occur at the nuclear membrane and not within the nucleus. Quantitative analysis demonstrated inefficiency in a number of steps including virus uptake and internalization, translocation of nucleocapsid across the nuclear membrane and antigen expression from intranuclear viral DNA.

Effect of 3′-azido-3′-deoxythymidine on replication of duck hepatitis B virus in vivo and in vitro

1989 ◽  
Vol 29 (4) ◽  
pp. 244-248 ◽  
Author(s):  
Hideaki Haritani ◽  
Toshikazu Uchida ◽  
Yasunori Okuda ◽  
Toshio Shikata
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Duck Hepatitis B Virus ◽  
Duck Hepatitis ◽  
B Virus

scholarly journals Dominant negative mutants of the duck hepatitis B virus core protein interfere with RNA pregenome packaging and viral DNA synthesis

Hepatology ◽  
1999 ◽  
Vol 30 (1) ◽  
pp. 308-315 ◽  
Author(s):  
Fritz von Weizsäcker ◽  
Josef Köck ◽  
Stefan Wieland ◽  
Wolf-Bernhard Offensperger ◽  
Hubert E. Blum
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Dna Synthesis ◽  
Core Protein ◽  
Dominant Negative ◽  
Viral Dna ◽  
Duck Hepatitis B Virus ◽  
Virus Core ◽  
Duck Hepatitis ◽  
B Virus

Inhibition of Duck Hepatitis B Virus Replication by 9-(2-Phosphonylmethoxyethyl)adenine, an Acyclic Phosphonate Nucleoside Analogue

1998 ◽  
Vol 42 (12) ◽  
pp. 3130-3135 ◽  
Author(s):  
A. J. Nicoll ◽  
D. L. Colledge ◽  
J. J. Toole ◽  
P. W. Angus ◽  
R. A. Smallwood ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Nucleoside Analogue ◽  
Viral Rna ◽  
Northern Hybridization ◽  
Duck Hepatitis B Virus ◽  
Protein Levels ◽  
Duck Hepatitis ◽  
Chronic Hepatitis B Virus ◽  
B Virus

ABSTRACT The use of regimens that use nucleoside analogues for the treatment of chronic hepatitis B virus infection is often limited because of their high relapse rates. This is thought to be due to the persistence of virus in nonhepatocyte reservoirs and/or the viral covalently closed circular (CCC) DNA species in the nucleus of infected hepatocytes. We have evaluated the novel nucleoside analogue 9-(2-phosphonylmethoxyethyl)adenine (PMEA) in the duck model of hepatitis B. Eight Pekin-Aylesbury ducks congenitally infected with the duck hepatitis B virus (DHBV) were treated with PMEA at a dosage of 15 mg/kg of body weight/day via the intraperitoneal route for 4 weeks. At the end of the treatment period, four animals were killed and the remainder were monitored for a further 4-week drug-free period before analysis. The results were compared with those for eight age-matched, untreated controls. The levels of viremia, the total intrahepatic DHBV load, and CCC DNA, viral RNA, and protein levels were measured by Southern hybridization, Northern hybridization, and immunoblotting of the appropriate specimen, respectively. Viral proteins and DNA were also measured by immunohistochemistry (IHC) and in situ hybridization (ISH) of sections of liver and pancreatic tissue. PMEA treatment reduced the viremia to undetectable levels, while the total viral DNA load in the liver was reduced by 95% compared to the control level. Viral RNA and protein levels decreased by approximately 30%. ISH and IHC confirmed the PMEA-related intrahepatic changes and established that the amount of virus in bile duct epithelial cells (BDEC) was reduced by 70% during therapy. During the follow-up period all parameters of active virological replication returned to those for the age-matched controls. PMEA had no significant effect upon the number of virus-infected islet or acinar cells in the pancreas. PMEA at a dosage of 15 mg/kg/day has potent activity against DHBV found within hepatocytes and BDEC and inhibits DHBV replication in BDEC.

Duck hepatitis B virus polymerase gene mutants associated with resistance to lamivudine have a decreased replication capacity in vitro and in vivo

2001 ◽  
Vol 34 (1) ◽  
pp. 114-122 ◽  
Author(s):  
Béatrice Seignères ◽  
Stéphanie Aguesse-Germon ◽  
Christian Pichoud ◽  
Isabelle Vuillermoz ◽  
Catherine Jamard ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Replication Capacity ◽  
Polymerase Gene ◽  
Duck Hepatitis B Virus ◽  
Duck Hepatitis ◽  
B Virus
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