title: Influenza A virus proteins PB1 and NS1 are subject to functionally important phosphorylation by protein kinase C.
abstract: The virulence of influenza A viruses depends on the activity of the viral RNA polymerase complex and viral regulatory phosphoproteins. We identified that the protein kinase C (PKC) inhibitor Gö6976 had a post-entry anti-influenza viral effect, by using a polymerase activity-based reporter assay. This inhibitory effect was observed for influenza virus-infected cells as well as for cells transiently transfected with constructs for the RNA polymerase complex. Importantly, the in vitro analysis of viral protein phosphorylation identified PKCalpha as a kinase phosphorylating PB1 and NS1, but not PB2, PA or NP. Gö6976 was able to block PKC-specific phosphorylation in vitro. Thus, our data suggest that PKC contributes to the phosphorylation of influenza PB1 and NS1 proteins which appears to be functionally relevant for both viral RNA polymerase activity and efficient viral replication.
authors.affiliation: Institute for Clinical and Molecular Virology, University of Erlangen-Nuremberg, Germany.
authors.forename: Shohreh
authors.initials: S
authors.lastname: Mahmoudian
authors.affiliation: Institute for Clinical and Molecular Virology, University of Erlangen-Nuremberg, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Auerochs
authors.affiliation: Institute for Clinical and Molecular Virology, University of Erlangen-Nuremberg, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Gröne
authors.affiliation: Institute for Clinical and Molecular Virology, University of Erlangen-Nuremberg, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Marschall
mesh_terms: D002227:Carbazoles / Q000494:pharmacology; D002460:Cell Line; D054884:Host-Pathogen Interactions; D006801:Humans; D009980:Influenza A virus / Q000502:physiology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D002227:Carbazoles; C085820:INS1 protein, influenza virus; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; C077346:influenza virus polymerase basic protein 1; C081021:Go 6976; D011493:Protein Kinase C