title: The proapoptotic influenza A virus protein PB1-F2 regulates viral polymerase activity by interaction with the PB1 protein.
abstract: The 11th influenza A virus protein PB1-F2 was previously shown to enhance apoptosis in response to cytotoxic stimuli. The 87 amino acid protein that is encoded by an alternative reading frame of the PB1 polymerase gene was described to localize to mitochondria consistent with its proapoptotic function. However, PB1-F2 is also found diffusely distributed in the cytoplasm and in the nucleus suggesting additional functions of the protein. Here we show that PB1-F2 colocalizes and directly interacts with the viral PB1 polymerase protein. Lack of PB1-F2 during infection resulted in an altered localization of PB1 and decreased viral polymerase activity. Consequently, mutant viruses devoid of a functional PB1-F2 reading frame exhibited a small plaque phenotype. Thus, we have identified a novel function of PB1-F2 as an indirect regulator of the influenza virus polymerase activity via its interaction with PB1.
authors.affiliation: Institute of Molecular Virology (IMV), Centre of Molecular Biology of Inflammation (ZMBE), Westfaelische-Wilhelms-University, 48161 Muenster, Germany.
authors.forename: Igor
authors.initials: I
authors.lastname: Mazur
authors.forename: Darisuren
authors.initials: D
authors.lastname: Anhlan
authors.forename: David
authors.initials: D
authors.lastname: Mitzner
authors.forename: Ludmilla
authors.initials: L
authors.lastname: Wixler
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schubert
authors.forename: Stephan
authors.initials: S
authors.lastname: Ludwig
mesh_terms: D000818:Animals; D002460:Cell Line; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D004285:Dogs; D006801:Humans; D012324:RNA-Dependent RNA Polymerase / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D014764:Viral Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: C442816:PB1-F2 protein, Influenza A virus; D014764:Viral Proteins; C077346:influenza virus polymerase basic protein 1; D012324:RNA-Dependent RNA Polymerase