Hepatitis B virus cccDNA clearance: killing for curing?
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Hepatitis B virus cccDNA clearance: killing for curing? / Dandri-Petersen, Maura; Petersen, Jorg.
In: HEPATOLOGY, Vol. 42, No. 6, 6, 2005, p. 1453-1455.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Hepatitis B virus cccDNA clearance: killing for curing?
AU - Dandri-Petersen, Maura
AU - Petersen, Jorg
PY - 2005
Y1 - 2005
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 42
SP - 1453
EP - 1455
JO - HEPATOLOGY
JF - HEPATOLOGY
SN - 0270-9139
IS - 6
M1 - 6
ER -