scholarly journals Duck hepatitis B virus covalently closed circular DNA appears to survive hepatocyte mitosis in the growing liver

Virology ◽  
2013 ◽  
Vol 446 (1-2) ◽  
pp. 357-364 ◽  
Author(s):  
Georget Y. Reaiche-Miller ◽  
Michael Thorpe ◽  
Huey Chi Low ◽  
Qiao Qiao ◽  
Catherine A. Scougall ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Duck Hepatitis B Virus ◽  
Circular Dna ◽  
Covalently Closed Circular Dna ◽  
Duck Hepatitis ◽  
B Virus

scholarly journals Age-Related Differences in Amplification of Covalently Closed Circular DNA at Early Times after Duck Hepatitis B Virus Infection of Ducks

2005 ◽  
Vol 79 (15) ◽  
pp. 9896-9903 ◽  
Author(s):  
Yong-Yuan Zhang ◽  
Daniel P. Theele ◽  
Jesse Summers
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Virus Replication ◽  
Duck Hepatitis B Virus ◽  
Circular Dna ◽  
Covalently Closed Circular Dna ◽  
Duck Hepatitis ◽  
Age Related ◽  
B Virus ◽  
Spread Of Infection

ABSTRACT Inoculation of 3-day-old (3D) or 3-week-old (3W) ducklings with duck hepatitis B virus results in chronic or transient infection, respectively. We previously showed that rapid production of neutralizing antibody following inoculation of 3W ducklings prevents virus from spreading in the liver and leads to a transient infection (Y.-Y. Zhang and J. Summers, J. Virol. 78:1195-1201, 2004). In this study we further investigated early events of viral infection in both 3D and 3W ducks. We present evidence that a lower level of virus replication in the hepatocytes of 3W birds is an additional factor that probably favors transient infection. We suggest that lower virus replication is due to a less rapid covalently closed circular DNA amplification, leading to lower viremias and a slower spread of infection in the liver, and that the slower spread of infection in 3W ducks makes the infection more sensitive to interruption by the host immune responses.

scholarly journals Half-Life of the Duck Hepatitis B Virus Covalently Closed Circular DNA Pool In Vivo following Inhibition of Viral Replication

2002 ◽  
Vol 76 (12) ◽  
pp. 6356-6363 ◽  
Author(s):  
William R. Addison ◽  
Kathie-Anne Walters ◽  
Winnie W. S. Wong ◽  
John S. Wilson ◽  
Danuta Madej ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Viral Replication ◽  
Duck Hepatitis B Virus ◽  
Circular Dna ◽  
Covalently Closed Circular Dna ◽  
Duck Hepatitis ◽  
B Virus ◽  
Dna Pool

ABSTRACT Covalently closed circular DNA (cccDNA) is a crucial intermediate in the replication of hepadnaviruses. We inhibited the replication of duck hepatitis B virus in congenitally infected ducks with a combination of lamivudine and a dideoxyguanosine prodrug. Inhibition of viral replication should prevent renewal of the cccDNA pool, and its decay was measured in liver biopsy samples collected over a 5-month period. In three ducks, the cccDNA pools declined exponentially, with half-lives ranging from 35 to 57 days. In two others, the pools declined exponentially for about 70 days but then stabilized at about 6 copies/diploid genome. The selection of drug-resistant virus mutants is an unlikely explanation for this unexpected stabilization of cccDNA levels. Liver sections stained for the cell division marker PCNA showed that animals in which cccDNA loss was continuous had significantly greater numbers of PCNA-positive nuclei than did those animals in which cccDNA levels had plateaued.

scholarly journals Mutations That Increase In Situ Priming Also Decrease Circularization for Duck Hepatitis B Virus

2001 ◽  
Vol 75 (14) ◽  
pp. 6492-6497 ◽  
Author(s):  
Daniel D. Loeb ◽  
Ru Tian
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Minus Strand ◽  
Complementary Sequence ◽  
Duck Hepatitis B Virus ◽  
Circular Dna ◽  
Duck Hepatitis ◽  
B Virus ◽  
Template Switch

ABSTRACT The process of hepadnavirus reverse transcription involves two template switches during the synthesis of plus-strand DNA. The first involves translocation of the plus-strand primer from its site of generation, the 3′ end of minus-strand DNA, to the complementary sequence DR2, located near the 5′ end of the minus-strand DNA. Plus strands initiated from DR2 are extended to the 5′ end of the minus-strand DNA. At this point, the 3′ end of the minus strand becomes the template via the second template switch, a process called circularization. Elongation of circularized plus-strand DNA generates relaxed circular DNA. Although most virions contain relaxed circular DNA, some contain duplex linear DNA. Duplex linear genomes are synthesized when the plus-strand primer is used at the site of its generation, the 3′ end of the minus-strand template. This type of synthesis is called in situ priming. Although in situ priming is normally low, in some duck hepatitis B virus mutants this type of priming is elevated. For example, mutations within the 3′ end of the minus-strand DNA can lead to increased levels of in situ priming. We report here that these same mutations result in a second defect, a less efficient template switch that circularizes the genome. Although it is not clear how these mutations affect both steps in DNA replication, our findings suggest a commonality in the mechanism of initiation of plus-strand synthesis and the template switch that circularizes the genome.

scholarly journals Analysis of Duck Hepatitis B Virus Reverse Transcription Indicates a Common Mechanism for the Two Template Switches during Plus-Strand DNA Synthesis

2002 ◽  
Vol 76 (6) ◽  
pp. 2763-2769 ◽  
Author(s):  
Michael B. Havert ◽  
Lin Ji ◽  
Daniel D. Loeb
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Dna Synthesis ◽  
Minus Strand ◽  
Duck Hepatitis B Virus ◽  
Circular Dna ◽  
Duck Hepatitis ◽  
Donor And Acceptor ◽  
B Virus ◽  
Template Switches

ABSTRACT The synthesis of the hepadnavirus relaxed circular DNA genome requires two template switches, primer translocation and circularization, during plus-strand DNA synthesis. Repeated sequences serve as donor and acceptor templates for these template switches, with direct repeat 1 (DR1) and DR2 for primer translocation and 5′r and 3′r for circularization. These donor and acceptor sequences are at, or near, the ends of the minus-strand DNA. Analysis of plus-strand DNA synthesis of duck hepatitis B virus (DHBV) has indicated that there are at least three other cis-acting sequences that make contributions during the synthesis of relaxed circular DNA. These sequences, 5E, M, and 3E, are located near the 5′ end, the middle, and the 3′ end of minus-strand DNA, respectively. The mechanism by which these sequences contribute to the synthesis of plus-strand DNA was unclear. Our aim was to better understand the mechanism by which 5E and M act. We localized the DHBV 5E element to a short sequence of approximately 30 nucleotides that is 100 nucleotides 3′ of DR2 on minus-strand DNA. We found that the new 5E mutants were partially defective for primer translocation/utilization at DR2. They were also invariably defective for circularization. In addition, examination of several new DHBV M variants indicated that they too were defective for primer translocation/utilization and circularization. Thus, this analysis indicated that 5E and M play roles in both primer translocation/utilization and circularization. In conjunction with earlier findings that 3E functions in both template switches, our findings indicate that the processes of primer translocation and circularization share a common underlying mechanism.

scholarly journals Entecavir Therapy Combined with DNA Vaccination for Persistent Duck Hepatitis B Virus Infection

2003 ◽  
Vol 47 (8) ◽  
pp. 2624-2635 ◽  
Author(s):  
Wendy K. Foster ◽  
Darren S. Miller ◽  
Patricia L. Marion ◽  
Richard J. Colonno ◽  
Ieva Kotlarski ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Antiviral Treatment ◽  
Dna Vaccination ◽  
Hepatitis B Virus Infection ◽  
Duck Hepatitis B Virus ◽  
Circular Dna ◽  
Duck Hepatitis ◽  
B Virus ◽  
Replicative Intermediates

ABSTRACT This study was designed to test the efficacy of antiviral treatment with entecavir (ETV) in combination with DNA vaccines expressing duck hepatitis B virus (DHBV) antigens as a therapy for persistent DHBV infection in ducks. Ducks were inoculated with 109 DHBV genomes at 7 days of age, leading to widespread infection of the liver and viremia within 7 days, and were then treated orally with either ETV (0.1 mg/kg of body weight/day) or distilled water from 21 days posthatch for 244 days. Treatment with ETV caused a 4-log drop in serum DHBV DNA levels within 80 days and a slower 2- to 3-log drop in serum DHBV surface antigen (DHBsAg) levels within 120 days. Following withdrawal of ETV, levels of serum DHBV DNA and DHBsAg rebounded to match those in the water-treated animals within 40 days. Sequential liver biopsy samples collected throughout the study showed that ETV treatment reduced DHBV DNA replicative intermediates 70-fold in the liver, while the level of the stable, template form, covalently closed circular DNA decreased only 4-fold. ETV treatment reduced both the intensity of antigen staining and the percentage of antigen-positive hepatocytes in the liver, but the intensity of antigen staining in bile duct cells appeared not to be effected. Intramuscular administration of five doses of a DNA vaccine expressing the DHBV presurface, surface, precore, and core antigens, both alone and concurrently with ETV treatment, on days 50, 64, 78, 127, and 141 did not result in any significant effect on viral markers.

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