Inhibition of protein kinase C phosphorylation of hepatitis B virus capsids inhibits virion formation and causes intracellular capsid accumulation

• Published in: Cellular microbiology Vol. 12; no. 7; pp. 962 - 975
• Main Authors: Wittkop, Linda, Schwarz, Alexandra, Cassany, Aurelia, Grün-Bernhard, Stefanie, Delaleau, Mildred, Rabe, Birgit, Cazenave, Christian, Gerlich, Wolfram, Glebe, Dieter, Kann, Michael
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.07.2010; Blackwell Publishing Ltd; Hindawi Limited; Wiley
• Subjects: Blotting, Southern; Blotting, Western; Capsid; Capsid - metabolism; Capsid protein; Capsid Proteins; Capsid Proteins - genetics; Capsid Proteins - metabolism; Capsids; DNA biosynthesis; Electrophoresis, Agar Gel; Genomes; Genotypes; Hep G2 Cells; Hepatitis B; Hepatitis B virus; Hepatitis B virus - genetics; Hepatitis B virus - metabolism; Humans; Life cycle; Life Sciences; Microbiology and Parasitology; Packaging; Phosphorylation; Protein Kinase C; Protein Kinase C - genetics; Protein Kinase C - metabolism; Replication; Virion; Virion - genetics; Virion - metabolism; Virions
• ISSN: 1462-5814; 1462-5822
• DOI: 10.1111/j.1462-5822.2010.01444.x

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 Cα, 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.