Influenza virus recruits host protein kinase C to control assembly and activity of its replication machinery
- Indian Institute of Technology Kharagpur, India
- University of Wisconsin-Madison, United States
Abstract
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.
Article and author information
Author details
Funding
Greater Milwaukee Foundation (Shaw Scientist Award)
- Andrew Mehle
American Lung Association (RG-310016)
- Andrew Mehle
National Institute of Allergy and Infectious Diseases (R01AI125271)
- Arindam Mondal
- Anthony R Dawson
- Elyse C Freiberger
- Andrew Mehle
National Institute of General Medical Sciences (R35GM118110)
- Gregory K Potts
- Joshua J Coon
National Institute of General Medical Sciences (R00GM088484)
- Arindam Mondal
- Andrew Mehle
National Institute of Allergy and Infectious Diseases (T32AI078985)
- Anthony R Dawson
Burroughs Wellcome Fund (Investigators in the Pathogenesis of Infectious Disease)
- Andrew Mehle
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Mondal et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Influenza virus recruits host protein kinase C to control assembly and activity of its replication machinery
eLife 6:e26910.
https://doi.org/10.7554/eLife.26910
