Duck hepatitis B virus covalently closed circular DNA appears to survive hepatocyte mitosis in the growing liver.
Nucleos(t)ide analogues that inhibit hepatitis B virus (HBV) DNA replication are typically used as monotherapy for chronically infected patients. Treatment with a nucleos(t)ide analogue eliminates most HBV DNA replication intermediates and produces a gradual decline in levels of covalently closed circular DNA (cccDNA), the template for viral RNA synthesis. It remains uncertain if levels of cccDNA decline primarily through hepatocyte death, or if loss also occurs during hepatocyte mitosis. To determine if cccDNA survives mitosis, growing ducklings infected with duck hepatitis B virus (DHBV) were treated with the nucleoside analogue, Entecavir. Viremia was suppressed at least 10(5)-fold, during a period when average liver mass increased 23-fold. Analysis of the data suggested that if cccDNA synthesis was completely inhibited, at least 49% of cccDNA survived hepatocyte mitosis. However, there was a large duck-to-duck variation in cccDNA levels, suggesting that low level cccDNA synthesis may contribute to this apparent survival through mitosis.
School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA 5005, Australia.
Georget Y
GY
Reaiche-Miller
Michael
M
Thorpe
Huey Chi
HC
Low
Qiao
Q
Qiao
Catherine A
CA
Scougall
William S
WS
Mason
Samuel
S
Litwin
Allison R
AR
Jilbert
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage; D004270:DNA, Circular / Q000302:isolation & purification; D004279:DNA, Viral / Q000302:isolation & purification*; D004372:Ducks; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015611:Hepatitis B Virus, Duck / Q000187:drug effects / Q000502:physiology*; D022781:Hepatocytes / Q000502:physiology / Q000821:virology*; D008099:Liver / Q000821:virology*; D008938:Mitosis; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D004270:DNA, Circular; D004279:DNA, Viral; C413685:entecavir; D006147:Guanine
Covalently closed circular DNA (cccDNA); Duck hepatitis B virus (DHBV); Entecavir (ETV); Hepatitis B virus (HBV); Hepatocyte mitosis; Nucleoside analogue; Survival or loss of cccDNA