title: The influenza virus PB1-F2 protein has interferon antagonistic activity.
abstract: PB1-F2 is a nonstructural protein of influenza viruses encoded by the PB1 gene segment from a +1 open reading frame. It has been shown that PB1-F2 contributes to viral pathogenicity, although the underlying mechanisms are still unclear. Induction of type I interferon (IFN) and the innate immune response are the first line of defense against viral infection. Here we show that influenza A viruses (IAVs) lacking the PB1-F2 protein induce an enhanced expression of IFN-β and IFN-stimulated genes in infected epithelial cells. Studying molecular mechanisms underlying the PB1-F2-mediated IFN antagonistic activity showed that PB1-F2 interferes with the RIG-I/MAVS protein complex thereby inhibiting the activation of the downstream transcription factor IFN regulatory factor 3. These findings were also reflected in in vivo studies demonstrating that infection with PR8 wild-type (wt) virus resulted in higher lung titers and a more severe onset of disease compared with infection with its PB1-F2-deficient counterpart. Accordingly, a much more pronounced infiltration of lungs with immune cells was detected in mice infected with the PB1-F2 wt virus. In summary, we demonstrate that the PB1-F2 protein of IAVs exhibits a type I IFN-antagonistic function by interfering with the RIG-I/MAVS complex, which contributes to an enhanced pathogenicity in vivo.
authors: Institute of Molecular Virology, Centre for Molecular Biology of Inflammation, Westfälische Wilhelms University, D-48149 Münster, Germany.
authors: Sabine E
authors: SE
authors: Dudek
authors: Ludmilla
authors: L
authors: Wixler
authors: Carolin
authors: C
authors: Nordhoff
authors: Alexandra
authors: A
authors: Nordmann
authors: Darisuren
authors: D
authors: Anhlan
authors: Viktor
authors: V
authors: Wixler
authors: Stephan
authors: S
authors: Ludwig
mesh_terms: D000818:Animals; D002460:Cell Line; D004285:Dogs; D006801:Humans; D007370:Interferon Type I / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D007370:Interferon Type I; C442816:PB1-F2 protein, Influenza A virus; D012333:RNA, Messenger; D014764:Viral Proteins