Lupberger J, Schaedler S, Peiran A, Hildt E. Identification and characterization of a novel bipartite nuclear localization signal in the hepatitis B virus polymerase. World J Gastroenterol 2013; 19(44): 8000-8010 [PMID: 24307793 DOI: 10.3748/wjg.v19.i44.8000]
Corresponding Author of This Article
Eberhard Hildt, Professor, Division of Virology, Paul-Ehrlich-Institute, Paul-Ehrlich-Str. 51-59, D-63225 Langen, Germany. eberhard.hildt@pei.de
Research Domain of This Article
Virology
Article-Type of This Article
Original Article
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World J Gastroenterol. Nov 28, 2013; 19(44): 8000-8010 Published online Nov 28, 2013. doi: 10.3748/wjg.v19.i44.8000
Identification and characterization of a novel bipartite nuclear localization signal in the hepatitis B virus polymerase
Joachim Lupberger, Stephanie Schaedler, Alexander Peiran, Eberhard Hildt
Joachim Lupberger, Stephanie Schaedler, Eberhard Hildt, Department of Medicine II, University of Freiburg, D-79106 Freiburg, Germany
Joachim Lupberger, Inserm, U748 Strasbourg, France
Alexander Peiran, Division of Virology, University Goettingen, 37073 Goettingen, Germany
Eberhard Hildt, Division of Virology, Paul-Ehrlich-Institute, D-63325 Langen, Germany
Author contributions: Lupberger J, Schaedler S, Peiran A and Hildt E performed experiments; Lupberger J and Hildt E designed the research and wrote the paper.
Supported by A Grant from DZIF to Hildt E
Correspondence to: Eberhard Hildt, Professor, Division of Virology, Paul-Ehrlich-Institute, Paul-Ehrlich-Str. 51-59, D-63225 Langen, Germany. eberhard.hildt@pei.de
Telephone: +49-610-3772140 Fax: +49-610-3771273
Received: July 19, 2013 Revised: September 12, 2013 Accepted: September 16, 2013 Published online: November 28, 2013 Processing time: 144 Days and 16.5 Hours
Core Tip
Core tip: The mechanism mediating import of the hepatitis B virus (HBV) genome into the nucleus is still not fully understood. We describe the identification and characterization of a bipartite nuclear localization signal (NLS) in the HBV polymerase that harbours a phosphorylation site for casein kinase II (CKII). Integrity of the phosphorylation site is crucial for the functionality of the NLS. Moreover, inhibition of CKII prevents karyopherin-α2 from binding to the polymerase and thereby the import of the polymerase is impaired. Analysing the viral life cycle we observed that inhibition of CKII blocks the import of the genome into the nucleus resulting in impaired cccDNA formation and so the establishment of the viral infection is prevented.
