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CDK/ERK-mediated phosphorylation of the human influenza A virus NS1 protein at threonine-215

Benjamin G Hale1, Axel Knebel, Catherine H Botting

  • 1Centre for Biomolecular Sciences, University of St. Andrews, North Haugh, St. Andrews, Fife KY16 9ST, UK.

Virology
|November 15, 2008
PubMed

Insights

Influenza A virus NS1 protein phosphorylation at threonine-215 by cellular kinases is crucial for early viral replication. This modification by cyclin-dependent kinases (CDKs) and extracellular signal-regulated kinases (ERKs) impacts virus propagation.

Area of Science:

  • Virology
  • Molecular and Cellular Biology
  • Biochemistry

Background:

  • Posttranslational modification of viral proteins by host enzymes is common in virus replication.
  • The influenza A virus NS1 protein plays multiple roles during infection.

Purpose of the Study:

  • To investigate the posttranslational modification of the influenza A virus NS1 protein.
  • To determine the role of NS1 protein phosphorylation at threonine-215 in viral replication.

Main Methods:

  • Site-directed mutagenesis to substitute threonine-215 with alanine in the NS1 protein.
  • Assessing viral propagation in cell culture.
  • In vitro kinase assays using proline-directed kinases.

Main Results:

  • Phosphorylation of the influenza A virus NS1 protein at threonine-215 was identified during infection.
  • Substitution of threonine-215 with alanine impaired early viral propagation.
  • Cyclin-dependent kinases (CDKs) and extracellular signal-regulated kinases (ERKs) were found to phosphorylate NS1 at threonine-215 in vitro.
  • The observed reduction in viral propagation was not linked to NS1's interferon antagonism or PI3K signaling.

Conclusions:

  • CDK/ERK-mediated phosphorylation of the influenza A virus NS1 protein at threonine-215 is important for efficient virus replication.
  • This specific posttranslational modification is a key factor in the influenza A virus life cycle.

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