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Volume 103, Issue 6

Comparative kinase activity profiling of pathogenic influenza A viruses reveals new anti- and pro-viral protein kinases No Access

Abstract

Constant evolution of influenza A viruses (IAVs) leads to the occurrence of new virus strains, which can cause epidemics and occasional pandemics. Here we compared two medically relevant IAVs, namely A/Hamburg/4/09 (H1N1) of the 2009 pandemic and the highly pathogenic avian IAV human isolate A/Thailand/1(KAN-1)/2004 (H5N1), for their ability to trigger intracellular phosphorylation patterns using a highly sensitive peptide-based kinase activity profiling approach. Virus-dependent tyrosine phosphorylations of substrate peptides largely overlap between the two viruses and are also strongly overrepresented in comparison to serine/threonine peptide phosphorylations. Both viruses trigger phosphorylations with distinct kinetics by overlapping and different kinases from which many form highly interconnected networks. As approximately half of the kinases forming a signalling hub have no known function for the IAV life cycle, we interrogated selected members of this group for their ability to interfere with IAV replication. These experiments revealed negative regulation of H1N1 and H5N1 replication by NUAK [novel (nua) kinase] kinases and by redundant ephrin A (EphA) receptor tyrosine kinases.

  • Received:
  • Accepted:
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Keyword(s): influenza A virus , kinase , phosphorylation , signalling and signalling hub
Funding
This study was supported by the:
  • Deutsche Forschungsgemeinschaft (Award SFB1213/2, project 268555672)
    • Principle Award Recipient: StephanPleschka
  • Deutsche Forschungsgemeinschaft (Award SFB1213/2, project 268555672)
    • Principle Award Recipient: M.Lienhard Schmitz
© 2022 The Authors
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/content/journal/jgv/10.1099/jgv.0.001762
2022-06-30
2024-04-20
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Comparative kinase activity profiling of pathogenic influenza A viruses reveals new anti- and pro-viral protein kinases
J. Gen. Virol. 103, 001762 (2022); https://doi.org/10.1099/jgv.0.001762
/content/journal/jgv/10.1099/jgv.0.001762
/content/journal/jgv/10.1099/jgv.0.001762
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