Influenza virus recruits host protein kinase C to control assembly and activity of its replication machinery
Arindam Mondal,
Anthony R Dawson,
Gregory K Potts,
Elyse C Freiberger,
Steven F Baker,
Lindsey A Moser,
Kristen A Bernard,
Joshua J Coon,
Andrew Mehle
Affiliations
Arindam Mondal
Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, United States
Anthony R Dawson
Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, United States; Graduate Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, United States
Gregory K Potts
Department of Chemistry, University of Wisconsin-Madison, Madison, United States
Elyse C Freiberger
Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, United States
Steven F Baker
Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, United States
Lindsey A Moser
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, United States
Kristen A Bernard
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, United States
Joshua J Coon
Department of Chemistry, University of Wisconsin-Madison, Madison, United States; Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, United States
Influenza virus expresses transcripts early in infection and transitions towards genome replication at later time points. This process requires de novo assembly of the viral replication machinery, large ribonucleoprotein complexes (RNPs) composed of the viral polymerase, genomic RNA and oligomeric nucleoprotein (NP). Despite the central role of RNPs during infection, the factors dictating where and when they assemble are poorly understood. Here we demonstrate that human protein kinase C (PKC) family members regulate RNP assembly. Activated PKCδ interacts with the polymerase subunit PB2 and phospho-regulates NP oligomerization and RNP assembly during infection. Consistent with its role in regulating RNP assembly, knockout of PKCδ impairs virus infection by selectively disrupting genome replication. However, primary transcription from pre-formed RNPs deposited by infecting particles is unaffected. Thus, influenza virus exploits host PKCs to regulate RNP assembly, a step required for the transition from primary transcription to genome replication during the infectious cycle.
