Hepatitis B virus (HBV) variants fluctuate in paired plasma and peripheral blood mononuclear cells among patient cohorts during different chronic hepatitis B (CHB) disease phases
Summary Hepatitis B virus is classically considered a hepatotropic virus but also infects peripheral blood mononuclear cells. Chronic hepatitis B has different disease phases modulated by host immunity. We compared HBV variability, drug resistance and immune escape mutations in the overlapping HBV p...
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Published in | Journal of viral hepatitis Vol. 22; no. 4; pp. 416 - 426 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Blackwell Publishing Ltd
01.04.2015
Wiley Subscription Services, Inc |
Subjects | |
Online Access | Get full text |
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Summary: | Summary
Hepatitis B virus is classically considered a hepatotropic virus but also infects peripheral blood mononuclear cells. Chronic hepatitis B has different disease phases modulated by host immunity. We compared HBV variability, drug resistance and immune escape mutations in the overlapping HBV polymerase/surface gene in plasma and peripheral blood mononuclear cells in different disease phases. Plasma and peripheral blood mononuclear cells were isolated from 22 treatment naïve patient cohorts (five inactive, six immune‐active, nine HBeAg negative and two immune‐tolerant). HBV was genotyped via line probe assay, hepatitis B surface antigen titres were determined by an in‐house immunoassay, and HBV DNA was quantified by kinetic PCR. The HBV polymerase/surface region, including full genome in some, was PCR‐amplified and cloned, and ~20 clones/sample were sequenced. The sequences were subjected to various mutational and phylogenetic analyses. Clonal sequencing showed that only three of 22 patients had identical HBV genotype profiles in both sites. In immune‐active chronic hepatitis B, viral diversity in plasma was higher compared with peripheral blood mononuclear cells. Mutations at residues, in a minority of clones, associated with drug resistance, and/or immune escape were found in both compartments but were more common in plasma. Immune escape mutations were more often observed in the peripheral blood mononuclear cells of immune‐active CHB carriers, compared with other disease phases. During all CHB disease phases, differences exist between HBV variants found in peripheral blood mononuclear cells and plasma. Moreover, these data indicate that HBV evolution occurs in a compartment and disease phase‐specific fashion. |
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Bibliography: | 2011 American Gastroenterology Association Research Scholar Award Table S1: Comparison of HBV genotype in plasma and PBMC of 22 treatment naïve CHB patients by clonal sequencing of the HBV P/RT and/or full genome (see Fig. ).Table S2: Comparison of HBV polymerase/RT and overlapping S region in plasma and PBMC by clonal sequence analysis in 22 treatment naïve patients with CHB and HBV full genome analysis in 3 CHB patients. ark:/67375/WNG-0RB538FH-D istex:D2490B612B615E1432E6329B0FEBB0D03F62021E 2010 American Association for the Study of Liver Disease Clinical and Translational Research Award (CSC) ArticleID:JVH12308 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1352-0504 1365-2893 |
DOI: | 10.1111/jvh.12308 |