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Quasdorff, M.* ; Hösel, M.* ; Odenthal, M.* ; Zedler, U.* ; Bohne, F.* ; Gripon, P.* ; Dienes, H.P.* ; Drebber, U.* ; Stippel, D.* ; Goeser, T.* ; Protzer, U.

A concerted action of HNF4alpha and HNF1alpha links hepatitis B virus replication to hepatocyte differentiation.

Cell. Microbiol. 10, 1478-1490 (2008)
DOI
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Hepatitis B virus (HBV) is an important human pathogen, which targets the liver extremely efficient, gaining access to hepatocytes by a so far unknown receptor and replicating in a hepatocyte-specific fashion. Cell differentiation seems to determine HBV replication. We here show that the level of hepatocyte differentiation, as indicated by hepatocyte polarization and metabolic activity, is closely correlated to the transcription of the HBV RNA pregenome. Pregenome transcription determined the level of HBV replication in various cell lines of hepatocellular origin and in primary human hepatocytes. A variety of hepatocyte-enriched nuclear factors have been described to regulate transcription of the pregenome, but it remained unknown which factors link HBV replication to hepatocyte differentiation. We determined that high expression levels of HNF4alpha but not its potential cofactors or other hepatocyte-enriched transcription factors were essential for efficient HBV replication, and link it to hepatocyte differentiation. HNF1alpha contributed to the control of HBV replication because it regulated the expression of HNF4alpha. Thus, a concerted action of HNF4alpha and HNF1alpha, which also determines morphological and functional differentiation of hepatocytes, links HBV replication to hepatocyte differentiation.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Sprache englisch
Veröffentlichungsjahr 2008
HGF-Berichtsjahr 2008
ISSN (print) / ISBN 1462-5814
e-ISSN 1462-5822
Zeitschrift Cellular Microbiology
Quellenangaben Band: 10, Heft: 7, Seiten: 1478-1490 Artikelnummer: , Supplement: ,
Verlag Wiley
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)
POF Topic(s) 30203 - Molecular Targets and Therapies
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-502700-003
DOI 10.1111/j.1462-5822.2008.01141.x
Scopus ID 45249096077
Erfassungsdatum 2008-09-09
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