title: Phosphorylation of influenza A virus NS1 protein at threonine 49 suppresses its interferon antagonistic activity.
abstract: Phosphorylation and dephosphorylation acts as a fundamental molecular switch that alters protein function and thereby regulates many cellular processes. The non-structural protein 1 (NS1) of influenza A virus is an important factor regulating virulence by counteracting cellular immune responses against viral infection. NS1 was shown to be phosphorylated at several sites; however, so far, no function has been conclusively assigned to these post-translational events yet. Here, we show that the newly identified phospho-site threonine 49 of NS1 is differentially phosphorylated in the viral replication cycle. Phosphorylation impairs binding of NS1 to double-stranded RNA and TRIM25 as well as complex formation with RIG-I, thereby switching off its interferon antagonistic activity. Because phosphorylation was shown to occur at later stages of infection, we hypothesize that at this stage other functions of the multifunctional NS1 beyond its interferon-antagonistic activity are needed.
authors.affiliation: Institute of Molecular Virology (IMV), Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms-University Muenster, Muenster, Germany.
authors.forename: Omer Abid
authors.initials: OA
authors.lastname: Kathum
authors.affiliation: Institute of Molecular Virology (IMV), Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms-University Muenster, Muenster, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Schräder
authors.affiliation: Institute of Molecular Virology (IMV), Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms-University Muenster, Muenster, Germany.
authors.forename: Darisuren
authors.initials: D
authors.lastname: Anhlan
authors.affiliation: Institute of Molecular Virology (IMV), Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms-University Muenster, Muenster, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Nordhoff
authors.affiliation: Institute of Molecular Virology (IMV), Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms-University Muenster, Muenster, Germany.
authors.forename: Swantje
authors.initials: S
authors.lastname: Liedmann
authors.affiliation: Institute of Experimental Pathology, Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms-University Muenster, Muenster, Germany.|Institute of Evolutionary and Medical Genomics, Brandenburg Medical School (MHB), Neuruppin, Germany.
authors.forename: Amit
authors.initials: A
authors.lastname: Pande
authors.affiliation: Institute of Hygiene, Westfaelische Wilhelms-University Muenster, Muenster, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Mellmann
authors.affiliation: Institute of Molecular Virology (IMV), Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms-University Muenster, Muenster, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Ehrhardt
authors.affiliation: Institute of Molecular Virology (IMV), Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms-University Muenster, Muenster, Germany.
authors.forename: Viktor
authors.initials: V
authors.lastname: Wixler
authors.affiliation: Institute of Molecular Virology (IMV), Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms-University Muenster, Muenster, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Ludwig
mesh_terms: D000818:Animals; D002460:Cell Line; D000071457:DEAD Box Protein 58 / Q000378:metabolism; D004285:Dogs; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism*; D061985:Madin Darby Canine Kidney Cells / Q000821:virology; D009154:Mutation; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011971:Receptors, Immunologic; D013912:Threonine / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D000070584:Tripartite Motif Proteins / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: C085820:INS1 protein, influenza virus; D011971:Receptors, Immunologic; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D017361:Viral Nonstructural Proteins; D013912:Threonine; D016899:Interferon-beta; C084523:TRIM25 protein, human; D044767:Ubiquitin-Protein Ligases; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58