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

B. G. Hale; A. Knebel; C. H. Botting; C. S. Galloway; B. L. Precious; David Jackson; R. M. Elliott; R. E. Randall

doi:10.1016/j.virol.2008.10.002

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

B. G. Hale, A. Knebel, C. H. Botting, C. S. Galloway, B. L. Precious, David Jackson, R. M. Elliott, R. E. Randall

Research output: Contribution to journal › Article › peer-review

67 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	6-11
Number of pages	6
Journal	Virology
Volume	383
Issue number	1
DOIs	https://doi.org/10.1016/j.virol.2008.10.002
Publication status	Published - 5 Jan 2009

Keywords

Amino Acid Substitution/genetics Cell Line Cyclin-Dependent Kinases/*metabolism Extracellular Signal-Regulated MAP Kinases/*metabolism Humans Influenza A virus/*physiology Mutagenesis, Site-Directed Phosphorylation Plaque Assay Threonine/metabolism Viral Nonstructural Proteins/*metabolism Virus Replication

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10.1016/j.virol.2008.10.002

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

abstract = "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.",

keywords = "Amino Acid Substitution/genetics Cell Line Cyclin-Dependent Kinases/*metabolism Extracellular Signal-Regulated MAP Kinases/*metabolism Humans Influenza A virus/*physiology Mutagenesis, Site-Directed Phosphorylation Plaque Assay Threonine/metabolism Viral Nonstructural Proteins/*metabolism Virus Replication",

author = "Hale, {B. G.} and A. Knebel and Botting, {C. H.} and Galloway, {C. S.} and Precious, {B. L.} and David Jackson and Elliott, {R. M.} and Randall, {R. E.}",

note = "Hale, Benjamin G Knebel, Axel Botting, Catherine H Galloway, Caroline S Precious, Bernard L Jackson, David Elliott, Richard M Randall, Richard E Medical Research Council/United Kingdom Wellcome Trust/United Kingdom Research Support, Non-U.S. Gov't United States Virology Virology. 2009 Jan 5;383(1):6-11. Epub 2008 Nov 13.",

year = "2009",

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doi = "10.1016/j.virol.2008.10.002",

language = "English",

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journal = "Virology",

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AU - Hale, B. G.

AU - Knebel, A.

AU - Botting, C. H.

AU - Galloway, C. S.

AU - Precious, B. L.

AU - Jackson, David

AU - Elliott, R. M.

AU - Randall, R. E.

N1 - Hale, Benjamin G Knebel, Axel Botting, Catherine H Galloway, Caroline S Precious, Bernard L Jackson, David Elliott, Richard M Randall, Richard E Medical Research Council/United Kingdom Wellcome Trust/United Kingdom Research Support, Non-U.S. Gov't United States Virology Virology. 2009 Jan 5;383(1):6-11. Epub 2008 Nov 13.

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AB - 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.

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JO - Virology

JF - Virology

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

Abstract

Keywords

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Virus NS1 - PI3 G0601126: Studies on the interaction of influenza virus NS1 protein with cellular P13-kinase

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

Abstract

Keywords

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Virus NS1 - PI3 G0601126: Studies on the interaction of influenza virus NS1 protein with cellular P13-kinase

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