| Autor: |
Volz, Tassilo, Lutgehetmann, Marc, Wachtler, Paul, Jacob, Anna, Quaas, Alexander, Murray, John M., Dandri, Maura, Petersen, Joerg |
| Předmět: |
|
| Zdroj: |
Gastroenterology (00165085); Sep2007, Vol. 133 Issue 3, p843-852, 10p |
| Abstrakt: |
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. [Copyright &y& Elsevier] |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
