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Hepatitis B virus covalently closed circular DNA homeostasis is independent of the lymphotoxin pathway during chronic HBV infection
Author(s) -
Meier M.A.,
Suslov A.,
Ketterer S.,
Heim M. H.,
Wieland S. F.
Publication year - 2017
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/jvh.12689
Subject(s) - lymphotoxin , apobec , hepatitis b virus , cccdna , lymphotoxin alpha , biology , lymphotoxin beta receptor , woodchuck hepatitis virus , virology , microbiology and biotechnology , hepadnaviridae , gene , virus , immunology , tumor necrosis factor alpha , genetics , hbsag , genome
Summary Current treatment options for patients with chronic hepatitis B virus ( HBV ) infection are not curative as they are not effective in eliminating covalently closed circular DNA (ccc DNA ). ccc DNA is a stable template for HBV transcription in the nucleus of hepatocytes and is thought to be one of the main factors responsible for HBV persistence. Recently, activation of the lymphotoxin beta receptor ( LT βR) has been shown to trigger degradation of ccc DNA through induction of cytidine deaminases of the APOBEC 3 family in HBV cell culture model systems. To assess the presence and relevance of such mechanisms in the liver of chronically HBV ‐infected patients, we compared intrahepatic ccc DNA levels with the expression levels of lymphotoxins and some of their target genes (eg APOBEC deaminases) in liver biopsy tissue. Our results confirm elevated gene expression levels of components of the lymphotoxin pathway including lymphotoxin alpha ( LT α), lymphotoxin beta ( LT β), APOBEC 3B (A3B) and APOBEC 3G (A3G) in the chronically HBV ‐infected liver compared to uninfected liver. Furthermore, expression levels of the genes of the APOBEC deaminase family were correlated with those of LT α and LT β gene expression, consistent with lymphotoxin‐mediated upregulation of APOBEC gene expression. However, intrahepatic ccc DNA and HBV replication levels were not correlated with LT α, LT β and APOBEC gene expression. In conclusion, these results suggest that although the lymphotoxin pathway is activated in the chronically HBV ‐infected liver, it has no major impact on HBV ccc DNA metabolism in chronic HBV infection.