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Impaired intrahepatic hepatitis B virus productivity contributes to low viremia in most HBeAg-negative patients.

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Impaired intrahepatic hepatitis B virus productivity contributes to low viremia in most HBeAg-negative patients. / Volz, Tassilo; Lütgehetmann, Marc; Wachtler, Paul; Jacob, Anna; Quaas, Alexander; Murray, John M; Dandri-Petersen, Maura; Petersen, Jörg.

In: GASTROENTEROLOGY, Vol. 133, No. 3, 3, 2007, p. 843-852.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Volz, T, Lütgehetmann, M, Wachtler, P, Jacob, A, Quaas, A, Murray, JM, Dandri-Petersen, M & Petersen, J 2007, 'Impaired intrahepatic hepatitis B virus productivity contributes to low viremia in most HBeAg-negative patients.', GASTROENTEROLOGY, vol. 133, no. 3, 3, pp. 843-852. <http://www.ncbi.nlm.nih.gov/pubmed/17854594?dopt=Citation>

APA

Volz, T., Lütgehetmann, M., Wachtler, P., Jacob, A., Quaas, A., Murray, J. M., Dandri-Petersen, M., & Petersen, J. (2007). Impaired intrahepatic hepatitis B virus productivity contributes to low viremia in most HBeAg-negative patients. GASTROENTEROLOGY, 133(3), 843-852. [3]. http://www.ncbi.nlm.nih.gov/pubmed/17854594?dopt=Citation

Vancouver

Volz T, Lütgehetmann M, Wachtler P, Jacob A, Quaas A, Murray JM et al. Impaired intrahepatic hepatitis B virus productivity contributes to low viremia in most HBeAg-negative patients. GASTROENTEROLOGY. 2007;133(3):843-852. 3.

Bibtex

@article{f2ddf2c5792845789395250b9ece42dd,
title = "Impaired intrahepatic hepatitis B virus productivity contributes to low viremia in most HBeAg-negative patients.",
abstract = "BACKGROUND ; AIMS: Knowledge of factors regulating transcriptional activity of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) may help in understanding mechanisms of viral decay and how these processes are thwarted in chronically HBV-infected patients. METHODS: Liver biopsies from 119 treatment-naive chronically infected patients (42 HBeAg-positive and 77 HBeAg-negative) were determined for HBV transcriptional and replicative activity. RESULTS: Significantly lower median serum HBV DNA (-4 log), intrahepatic HBV DNA (-2 log), and cccDNA (-1 log) amounts were measured in HBeAg-negative versus HBeAg-positive patients. Despite a good correlation found between intrahepatic amounts of progeny virions and serum HBV DNA in all patients, cccDNA levels did not correlate with serum titers in HBeAg-negative individuals. Analysis of HBV RNA transcripts showed that impaired virion productivity in HBeAg-negative individuals was due to lower steady-state levels of pregenomic RNA produced per cccDNA. Interestingly, preS/S RNA levels and serum HBsAg concentrations did not differ between HBeAg-positive and HBeAg-negative patients when normalized for cccDNA contents, showing that subviral particle production was not impaired in HBeAg-negative patients and correlated with cccDNA levels. Although the majority of HBeAg-negative individuals harbored cccDNA with common precore and/or basal core promoter mutations, occurrence of these variants was not responsible for reduced viral replication. Instead, replacement of wild-type cccDNA with core promoter mutants reestablished high virion productivity. CONCLUSIONS: Lower viremia in HBeAg-negative individuals is not only due to lower cccDNA content but also to impaired virion productivity, which can arise without emergence of HBeAg variants and without affecting HBsAg production.",
author = "Tassilo Volz and Marc L{\"u}tgehetmann and Paul Wachtler and Anna Jacob and Alexander Quaas and Murray, {John M} and Maura Dandri-Petersen and J{\"o}rg Petersen",
year = "2007",
language = "Deutsch",
volume = "133",
pages = "843--852",
journal = "GASTROENTEROLOGY",
issn = "0016-5085",
publisher = "W.B. Saunders Ltd",
number = "3",

}

RIS

TY - JOUR

T1 - Impaired intrahepatic hepatitis B virus productivity contributes to low viremia in most HBeAg-negative patients.

AU - Volz, Tassilo

AU - Lütgehetmann, Marc

AU - Wachtler, Paul

AU - Jacob, Anna

AU - Quaas, Alexander

AU - Murray, John M

AU - Dandri-Petersen, Maura

AU - Petersen, Jörg

PY - 2007

Y1 - 2007

N2 - BACKGROUND ; AIMS: Knowledge of factors regulating transcriptional activity of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) may help in understanding mechanisms of viral decay and how these processes are thwarted in chronically HBV-infected patients. METHODS: Liver biopsies from 119 treatment-naive chronically infected patients (42 HBeAg-positive and 77 HBeAg-negative) were determined for HBV transcriptional and replicative activity. RESULTS: Significantly lower median serum HBV DNA (-4 log), intrahepatic HBV DNA (-2 log), and cccDNA (-1 log) amounts were measured in HBeAg-negative versus HBeAg-positive patients. Despite a good correlation found between intrahepatic amounts of progeny virions and serum HBV DNA in all patients, cccDNA levels did not correlate with serum titers in HBeAg-negative individuals. Analysis of HBV RNA transcripts showed that impaired virion productivity in HBeAg-negative individuals was due to lower steady-state levels of pregenomic RNA produced per cccDNA. Interestingly, preS/S RNA levels and serum HBsAg concentrations did not differ between HBeAg-positive and HBeAg-negative patients when normalized for cccDNA contents, showing that subviral particle production was not impaired in HBeAg-negative patients and correlated with cccDNA levels. Although the majority of HBeAg-negative individuals harbored cccDNA with common precore and/or basal core promoter mutations, occurrence of these variants was not responsible for reduced viral replication. Instead, replacement of wild-type cccDNA with core promoter mutants reestablished high virion productivity. CONCLUSIONS: Lower viremia in HBeAg-negative individuals is not only due to lower cccDNA content but also to impaired virion productivity, which can arise without emergence of HBeAg variants and without affecting HBsAg production.

AB - BACKGROUND ; AIMS: Knowledge of factors regulating transcriptional activity of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) may help in understanding mechanisms of viral decay and how these processes are thwarted in chronically HBV-infected patients. METHODS: Liver biopsies from 119 treatment-naive chronically infected patients (42 HBeAg-positive and 77 HBeAg-negative) were determined for HBV transcriptional and replicative activity. RESULTS: Significantly lower median serum HBV DNA (-4 log), intrahepatic HBV DNA (-2 log), and cccDNA (-1 log) amounts were measured in HBeAg-negative versus HBeAg-positive patients. Despite a good correlation found between intrahepatic amounts of progeny virions and serum HBV DNA in all patients, cccDNA levels did not correlate with serum titers in HBeAg-negative individuals. Analysis of HBV RNA transcripts showed that impaired virion productivity in HBeAg-negative individuals was due to lower steady-state levels of pregenomic RNA produced per cccDNA. Interestingly, preS/S RNA levels and serum HBsAg concentrations did not differ between HBeAg-positive and HBeAg-negative patients when normalized for cccDNA contents, showing that subviral particle production was not impaired in HBeAg-negative patients and correlated with cccDNA levels. Although the majority of HBeAg-negative individuals harbored cccDNA with common precore and/or basal core promoter mutations, occurrence of these variants was not responsible for reduced viral replication. Instead, replacement of wild-type cccDNA with core promoter mutants reestablished high virion productivity. CONCLUSIONS: Lower viremia in HBeAg-negative individuals is not only due to lower cccDNA content but also to impaired virion productivity, which can arise without emergence of HBeAg variants and without affecting HBsAg production.

M3 - SCORING: Zeitschriftenaufsatz

VL - 133

SP - 843

EP - 852

JO - GASTROENTEROLOGY

JF - GASTROENTEROLOGY

SN - 0016-5085

IS - 3

M1 - 3

ER -