Document Detail

Hepatitis B virus X protein is essential to initiate and maintain virus replication after infection.
MedLine Citation:
PMID:  21376091     Owner:  NLM     Status:  MEDLINE    
BACKGROUND & AIMS: The molecular biology of hepatitis B virus (HBV) has been extensively studied but the exact role of the hepatitis B X protein (HBx) in the context of natural HBV infections remains unknown.
METHODS: Primary human hepatocytes and differentiated HepaRG cells allowing conditional trans complementation of HBx were infected with wild type (HBV(wt)) or HBx deficient (HBV(x-)) HBV particles and establishment of HBV replication was followed.
RESULTS: We observed that cells inoculated with HBx-deficient HBV particles (HBV(x-)) did not lead to productive HBV infection contrary to cells inoculated with wild type HBV particles (HBV(wt)). Although equal amounts of nuclear covalently closed circular HBV-DNA (cccDNA) demonstrated comparable uptake and nuclear import, active transcription was only observed from HBV(wt) genomes. Trans-complementation of HBx was able to rescue transcription from the HBV(x-) genome and led to antigen and virion secretion, even weeks after infection. Constant expression of HBx was necessary to maintain HBV antigen expression and replication. Finally, we demonstrated that HBx is not packaged into virions during assembly but is expressed after infection within the new host cell to allow epigenetic control of HBV transcription from cccDNA.
CONCLUSIONS: Our results demonstrate that HBx is required to initiate and maintain HBV replication and highlight HBx as the key regulator during the natural infection process.
Julie Lucifora; Silke Arzberger; David Durantel; Laura Belloni; Michel Strubin; Massimo Levrero; Fabien Zoulim; Olivier Hantz; Ulrike Protzer
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-03-02
Journal Detail:
Title:  Journal of hepatology     Volume:  55     ISSN:  1600-0641     ISO Abbreviation:  J. Hepatol.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-10-19     Completed Date:  2012-03-06     Revised Date:  2012-08-24    
Medline Journal Info:
Nlm Unique ID:  8503886     Medline TA:  J Hepatol     Country:  England    
Other Details:
Languages:  eng     Pagination:  996-1003     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Institute of Virology, Technische Universität München/Helmholtz Zentrum München, Trogerstrasse, 30, 81675 Munich, Germany.
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MeSH Terms
DNA, Circular / metabolism*
DNA, Viral / metabolism*
Hep G2 Cells
Hepatitis B / virology*
Hepatitis B Surface Antigens / metabolism
Hepatitis B e Antigens / metabolism
Hepatitis B virus / genetics,  physiology*
Trans-Activators / genetics,  physiology*
Transcription, Genetic
Virus Replication*
Reg. No./Substance:
0/DNA, Circular; 0/DNA, Viral; 0/Hepatitis B Surface Antigens; 0/Hepatitis B e Antigens; 0/Trans-Activators; 0/hepatitis B virus X protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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