title: Inhibition of protein kinase C phosphorylation of hepatitis B virus capsids inhibits virion formation and causes intracellular capsid accumulation.
abstract: Capsids of hepatitis B virus and other hepadnaviruses contain a cellular protein kinase, which phosphorylates the capsid protein. Some phosphorylation sites are shown to be essential for distinct steps of viral replication as pregenome packaging or plus strand DNA synthesis. Although different protein kinases have been reported to phosphorylate the capsid protein, varying experimental approaches do not allow direct comparison. Furthermore, the activity of a specific protein kinase has not yet been correlated to steps in the hepadnaviral life cycle. In this study we show that capsids from various sources encapsidate active protein kinase Calpha, irrespective of hepatitis B virus genotype and host cell. Treatment of a virion expressing cell line with a pseudosubstrate inhibitor showed that inhibition of protein kinase C phosphorylation did not affect genome maturation but resulted in capsid accumulation and inhibited virion release to the medium. Our results imply that different protein kinases have distinct functions within the hepadnaviral life cycle.
authors.affiliation: Institute of Medical Virology, Justus Liebig University, Frankfurter Strasse 107, D-35392 Giessen, Germany.
authors.forename: Linda
authors.initials: L
authors.lastname: Wittkop
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schwarz
authors.forename: Aurelia
authors.initials: A
authors.lastname: Cassany
authors.forename: Stefanie
authors.initials: S
authors.lastname: Grün-Bernhard
authors.forename: Mildred
authors.initials: M
authors.lastname: Delaleau
authors.forename: Birgit
authors.initials: B
authors.lastname: Rabe
authors.forename: Christian
authors.initials: C
authors.lastname: Cazenave
authors.forename: Wolfram
authors.initials: W
authors.lastname: Gerlich
authors.forename: Dieter
authors.initials: D
authors.lastname: Glebe
authors.forename: Michael
authors.initials: M
authors.lastname: Kann
mesh_terms: D015139:Blotting, Southern; D015153:Blotting, Western; D002213:Capsid / Q000378:metabolism*; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D004587:Electrophoresis, Agar Gel; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000235:genetics / Q000378:metabolism*
chemical_list: D036022:Capsid Proteins; D011493:Protein Kinase C