The influenza virus PB1-F2 protein has interferon antagonistic activity
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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.
©2011 by Walter de Gruyter Berlin Boston
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Articles in the same Issue
- Reviews
- Squalene monooxygenase – a target for hypercholesterolemic therapy
- Cysteine proteinase SpeB from Streptococcus pyogenes – a potent modifier of immunologically important host and bacterial proteins
- Protein Structure and Function
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- Cloning, expression, characterization and inhibition studies on trypanothione synthetase, a drug target enzyme, from Leishmania donovani
- Cell Biology and Signaling
- Glucagon counteracts interleukin-6-dependent gene expression by redundant action of Epac and PKA
- The influenza virus PB1-F2 protein has interferon antagonistic activity
- Somatotropic gene response to recombinant growth hormone treatment in buffalo leucocytes
- Ammonia increases nitric oxide, free Zn2+, and metallothionein mRNA expression in cultured rat astrocytes
- Proteolysis
- Expression pattern of cathepsin W isoforms in peripheral blood and gastroesophageal mucosa of patients with gastroesophageal reflux disease
