title: Covalently closed circular DNA is the predominant form of duck hepatitis B virus DNA that persists following transient infection.
abstract: Residual hepatitis B virus (HBV) DNA can be detected in serum and liver after apparent recovery from transient infection. However, it is not known if this residual HBV DNA represents ongoing viral replication and antigen expression. In the current study, ducks inoculated with duck hepatitis B virus (DHBV) were monitored for residual DHBV DNA following recovery from transient infection until 9 months postinoculation (p.i.). Resolution of DHBV infection occurred in 13 out of 15 ducks by 1-month p.i., defined as clearance of DHBV surface antigen-positive hepatocytes from the liver and development of anti-DHBV surface antibodies. At 9 months p.i., residual DHBV DNA was detected using nested PCR in 10/11 liver, 7/11 spleen, 2/11 kidney, 1/11 heart, and 1/11 adrenal samples. Residual DHBV DNA was not detected in serum or peripheral blood mononuclear cells. Within the liver, levels of residual DHBV DNA were 0.0024 to 0.016 copies per cell, 40 to 80% of which were identified as covalently closed circular viral DNA by quantitative PCR assay. This result, which was confirmed by Southern blot hybridization, is consistent with suppressed viral replication or inactive infection. Samples of liver and spleen cells from recovered animals did not transmit DHBV infection when inoculated into 1- to 2-day-old ducklings, and immunosuppressive treatment of ducks with cyclosporine and dexamethasone for 4 weeks did not alter levels of residual DHBV DNA in the liver. These findings further characterize a second form of hepadnavirus persistence in a suppressed or inactive state, quite distinct from the classical chronic carrier state.
authors.affiliation: School of Molecular and Biomedical Science, University of Adelaide, North Terrace, Adelaide, South Australia 5000, Australia.
authors.forename: Marc F
authors.initials: MF
authors.lastname: Le Mire
authors.forename: Darren S
authors.initials: DS
authors.lastname: Miller
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Foster
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Burrell
authors.forename: Allison R
authors.initials: AR
authors.lastname: Jilbert
mesh_terms: D000311:Adrenal Glands / Q000821:virology; D000818:Animals; D004270:DNA, Circular / Q000032:analysis* / Q000302:isolation & purification; D004279:DNA, Viral / Q000032:analysis* / Q000302:isolation & purification; D004372:Ducks; D016679:Genome, Viral; D006321:Heart / Q000821:virology; D018347:Hepadnaviridae Infections / Q000821:virology*; D015611:Hepatitis B Virus, Duck / Q000235:genetics* / Q000502:physiology*; D006524:Hepatitis, Viral, Animal / Q000821:virology*; D007668:Kidney / Q000821:virology; D007963:Leukocytes, Mononuclear / Q000821:virology; D008099:Liver / Q000821:virology; D016133:Polymerase Chain Reaction; D013154:Spleen / Q000821:virology
chemical_list: D004270:DNA, Circular; D004279:DNA, Viral