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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred


IMPACT FACTOR 2018: 3.014
5-year IMPACT FACTOR: 3.162

CiteScore 2018: 3.09

SCImago Journal Rank (SJR) 2018: 1.482
Source Normalized Impact per Paper (SNIP) 2018: 0.820

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1437-4315
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Volume 392, Issue 12

Issues

The influenza virus PB1-F2 protein has interferon antagonistic activity

Sabine E. Dudek
  • Institute of Molecular Virology, Centre for Molecular Biology of Inflammation, Westfälische Wilhelms University, D-48149 Münster, Germany
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/ Ludmilla Wixler
  • Institute of Molecular Virology, Centre for Molecular Biology of Inflammation, Westfälische Wilhelms University, D-48149 Münster, Germany
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/ Carolin Nordhoff
  • Institute of Molecular Virology, Centre for Molecular Biology of Inflammation, Westfälische Wilhelms University, D-48149 Münster, Germany
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/ Alexandra Nordmann
  • Institute of Molecular Virology, Centre for Molecular Biology of Inflammation, Westfälische Wilhelms University, D-48149 Münster, Germany
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/ Darisuren Anhlan
  • Institute of Molecular Virology, Centre for Molecular Biology of Inflammation, Westfälische Wilhelms University, D-48149 Münster, Germany
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/ Viktor Wixler
  • Institute of Molecular Virology, Centre for Molecular Biology of Inflammation, Westfälische Wilhelms University, D-48149 Münster, Germany
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/ Stephan Ludwig
  • Institute of Molecular Virology, Centre for Molecular Biology of Inflammation, Westfälische Wilhelms University, D-48149 Münster, Germany
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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.

Keywords: IFN-antagonist; MAVS; PB1-F2; RIG-I

About the article

Corresponding author


Received: 2011-06-22

Accepted: 2011-09-23

Published in Print: 2011-12-01


Citation Information: Biological Chemistry, Volume 392, Issue 12, Pages 1135–1144, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2011.174.

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