1. Microbiology and Infectious Disease

Influenza virus recruits host protein kinase C to control assembly and activity of its replication machinery

  1. Arindam Mondal
  2. Anthony R Dawson
  3. Gregory K Potts
  4. Elyse C Freiberger
  5. Steven F Baker
  6. Lindsey A Moser
  7. Kristen A Bernard
  8. Joshua J Coon
  9. Andrew Mehle  Is a corresponding author
  1. Indian Institute of Technology Kharagpur, India
  2. University of Wisconsin-Madison, United States
https://doi.org/10.7554/eLife.26910
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  1. Arindam Mondal
  2. Anthony R Dawson
  3. Gregory K Potts
  4. Elyse C Freiberger
  5. Steven F Baker
  6. Lindsey A Moser
  7. Kristen A Bernard
  8. Joshua J Coon
  9. Andrew Mehle
(2017)
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
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  3. Download .RIS

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

  1. Arindam Mondal

    School of Bioscience, Indian Institute of Technology Kharagpur, Kharagpur, India
    Competing interests
    The authors declare that no competing interests exist.

  2. Anthony R Dawson

    Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Gregory K Potts

    Department of Chemistry, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Elyse C Freiberger

    Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Steven F Baker

    Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Lindsey A Moser

    Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Kristen A Bernard

    Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Joshua J Coon

    Department of Chemistry, University of Wisconsin-Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.

  9. Andrew Mehle

    Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, United States
    For correspondence
    amehle@wisc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6060-4330

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.

Reviewing Editor

  1. Karla Kirkegaard, Stanford University School of Medicine, United States

Version history

  1. Received: March 17, 2017
  2. Accepted: July 29, 2017
  3. Accepted Manuscript published: July 31, 2017 (version 1)
  4. Version of Record published: August 29, 2017 (version 2)

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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  1. Arindam Mondal
  2. Anthony R Dawson
  3. Gregory K Potts
  4. Elyse C Freiberger
  5. Steven F Baker
  6. Lindsey A Moser
  7. Kristen A Bernard
  8. Joshua J Coon
  9. Andrew Mehle
(2017)
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

Share this article

https://doi.org/10.7554/eLife.26910

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