Document Detail


The myristoylated preS1-domain of the hepatitis B virus L-protein mediates specific binding todifferentiated hepatocytes.
MedLine Citation:
PMID:  23213046     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Chronic infection with the human hepatitis B virus (HBV) is a global health problemand themain cause ofprogressive liver diseases. HBVexhibits a narrow host range,replicatingprimarilyin hepatocytes. Both, host and hepatocyte specificity presumably involvespecific receptorinteractionson the target cell; however, direct evidence for this hypothesis is missing. Followingthe observation that HBV entry isspecifically blocked by L-protein-derivedpreS1-lipopeptides,we visualizedspecific HBV receptor/ligand complexeson hepatic cells and quantifiedthe turnover kinetics.Using FITC-labeled,myristoylated HBVpreS1-peptides we demonstrate (i) the presence of a highly specific HBVreceptor onthe plasma membrane of HBV-susceptible primary human and tupaiahepatocytes,HepaRG cellsbut also on hepatocytes from the non-susceptible species mouse, rat, rabbit, dog, (ii) the requirement of a differentiated state of the hepatocyte for specific preS1-binding, (iii) the lack of detectable amounts of the receptoron HepG2 and HuH7cells, (iv) a slow receptor turnover at the hepatocyte membraneand (v) an association of the receptorwith actin microfilaments.The presence of the preS1-receptor in primaryhepatocytes fromsomenon-HBV-susceptible species indicates that the lack of susceptibility of these cells isowedtoa post binding step.Together with complementary in vivo studies(Schiecket al., in revision) we conclude thatHBV hepatotropism is mediated by the highly selective expression of a yet unknown receptor on differentiatedhepatocytes,while species specificity of the HBV infection requires selective downstream events, e.g. the presence of host dependency- or the absence of host restriction-factors.The criteria defined here will allow narrowing down reasonable receptor candidates and provide a binding assay for HBV-receptor expression screens in hepatic cells. (HEPATOLOGY 2012.).
Authors:
Anja Meier; Stefan Mehrle; Thomas S Weiss; Walter Mier; Stephan Urban
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-5
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  -     ISSN:  1527-3350     ISO Abbreviation:  Hepatology     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 American Association for the Study of Liver Diseases.
Affiliation:
Department ofInfectious Diseases,Molecular Virology, University Hospital Heidelberg, ImNeuenheimer Feld 345, D-69120 Heidelberg, Germany.
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