CDK/ERK-mediated phosphorylation of the human influenza A virus NS1 protein at threonine-215.
Posttranslational modification of viral proteins by cellular enzymes is a feature of many virus replication strategies. Here, we report that during infection the multifunctional human influenza A virus NS1 protein is phosphorylated at threonine-215. Substitution of alanine for threonine at this position reduced early viral propagation, an effect apparently unrelated to NS1 antagonizing host interferon responses or activating phosphoinositide 3-kinase signaling. In vitro, a subset of cellular proline-directed kinases, including cyclin dependent kinases (CDKs) and extracellular signal-regulated kinases (ERKs), potently phosphorylated NS1 protein at threonine-215. Our data suggest that CDK/ERK-mediated phosphorylation of NS1 at threonine-215 is important for efficient virus replication.
Hale
Benjamin G
BG
Centre for Biomolecular Sciences, University of St. Andrews, North Haugh, St. Andrews, Fife KY16 9ST, UK.
Knebel
Axel
A
Botting
Catherine H
CH
Galloway
Caroline S
CS
Precious
Bernard L
BL
Jackson
David
D
Elliott
Richard M
RM
Randall
Richard E
RE
D019943:Amino Acid Substitution / Q000235:genetics; D002460:Cell Line; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D009980:Influenza A virus / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D013912:Threonine / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000378:metabolism*; D010948:Viral Plaque Assay; D014779:Virus Replication
C085820:INS1 protein, influenza virus; D017361:Viral Nonstructural Proteins; D013912:Threonine; D018844:Cyclin-Dependent Kinases; D048049:Extracellular Signal-Regulated MAP Kinases