Document Detail

Hepatitis B virus cccDNA clearance: killing for curing?
MedLine Citation:
PMID:  16317676     Owner:  NLM     Status:  MEDLINE    
Chronic hepadnavirus infections cause liver damage with ongoing death and regeneration of hepatocytes. In the present study, we set out to quantify the extent of liver turnover by measuring the clonal proliferation of hepatocytes by using integrated viral DNA as a genetic marker for individual hepatocyte lineages. Liver tissue from woodchucks with chronic woodchuck hepatitis virus (WHV) infection was assayed for randomly integrated viral DNA by using inverse PCR. Serial endpoint dilution of viral-cell junction fragments into 96-well plates, followed by nested PCR and DNA sequencing, was used to determine the copy number of specific viral cell junctions as a measure of the clonal distribution of infected cell subpopulations. The results indicated that the livers contained a minimum of 100,000 clones of >1,000 cells containing integrated DNA, representing at least 0.2% of the hepatocyte population of the liver. Because cells with integrated WHV DNA comprised only 1-2% of total liver cells, it is likely that the total number of clones far exceeds this estimate, with as much as one half of the liver derived from high copy clones of >1,000 cells. It may be inferred that these clones have a strong selective growth or survival advantage. The results provide evidence for a large amount of hepatocyte proliferation and selection having occurred during the period of chronic WHV infection (approximately 1.5 years) in these animals.
Maura Dandri; Jorg Petersen
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  42     ISSN:  0270-9139     ISO Abbreviation:  Hepatology     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2005-12-05     Completed Date:  2005-12-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1453-5     Citation Subset:  IM    
Medizinische Klinik I, Gastroenterologie, Hepatologie und Infektiologie, Universit?tsklinikum Hamburg--Eppendorf, Germany.
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MeSH Terms
Cell Proliferation
DNA, Circular / metabolism*
DNA, Viral / metabolism*
Hepatitis B Virus, Woodchuck*
Hepatitis B, Chronic / pathology*,  virology*
Hepatocytes / pathology*,  virology
Virus Integration
Reg. No./Substance:
0/DNA, Circular; 0/DNA, Viral

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