Influenza virus recruits host protein kinase C to control assembly and activity of its replication machinery
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 n...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-07-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/26910 |
| _version_ | 1811252936263598080 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Arindam Mondal |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T16:43:14Z |
| format | Article |
| id | doaj.art-596f73a4764947edb237f877a986d628 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:43:14Z |
| publishDate | 2017-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-596f73a4764947edb237f877a986d6282022-12-22T03:24:42ZengeLife Sciences Publications LtdeLife2050-084X2017-07-01610.7554/eLife.26910Influenza virus recruits host protein kinase C to control assembly and activity of its replication machineryArindam Mondal0Anthony R Dawson1Gregory K Potts2Elyse C Freiberger3Steven F Baker4Lindsey A Moser5Kristen A Bernard6Joshua J Coon7Andrew Mehle8https://orcid.org/0000-0001-6060-4330Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, United StatesMedical Microbiology and Immunology, University of Wisconsin-Madison, Madison, United States; Graduate Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Madison, United StatesDepartment of Chemistry, University of Wisconsin-Madison, Madison, United StatesDepartment of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, United StatesMedical Microbiology and Immunology, University of Wisconsin-Madison, Madison, United StatesDepartment of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, United StatesDepartment of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, United StatesDepartment of Chemistry, University of Wisconsin-Madison, Madison, United States; Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, United StatesMedical Microbiology and Immunology, University of Wisconsin-Madison, Madison, United StatesInfluenza 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.https://elifesciences.org/articles/26910influenza virusnucleoproteinpolymerasekinaseprotein kinase C |
| spellingShingle | 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 Influenza virus recruits host protein kinase C to control assembly and activity of its replication machinery eLife influenza virus nucleoprotein polymerase kinase protein kinase C |
| title | Influenza virus recruits host protein kinase C to control assembly and activity of its replication machinery |
| title_full | Influenza virus recruits host protein kinase C to control assembly and activity of its replication machinery |
| title_fullStr | Influenza virus recruits host protein kinase C to control assembly and activity of its replication machinery |
| title_full_unstemmed | Influenza virus recruits host protein kinase C to control assembly and activity of its replication machinery |
| title_short | Influenza virus recruits host protein kinase C to control assembly and activity of its replication machinery |
| title_sort | influenza virus recruits host protein kinase c to control assembly and activity of its replication machinery |
| topic | influenza virus nucleoprotein polymerase kinase protein kinase C |
| url | https://elifesciences.org/articles/26910 |
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