Journal article
Influenza Virus Protein PB1-F2 Inhibits the Induction of Type I Interferon by Binding to MAVS and Decreasing Mitochondrial Membrane Potential
Journal of virology, Vol.86(16), pp.8359-8366
08/2012
DOI: 10.1128/JVI.01122-12
PMCID: PMC3421771
PMID: 22674996
Abstract
PB1-F2 is a small, 87- to 90-amino-acid-long protein encoded by the +1 alternate open reading frame of the PB1 gene of most influenza A virus strains. It has been shown to contribute to viral pathogenicity in a host- and strain-dependent manner, and we have previously discovered that a serine at position 66 (66S) in the PB1-F2 protein increases virulence of the 1918 and H5N1 pandemic viruses. Recently, we have shown that PB1-F2 inhibits the induction of type I interferon (IFN) at the level of the MAVS adaptor protein. However, the molecular mechanism for the IFN antagonist function of PB1-F2 has remained unclear. In the present study, we demonstrated that the C-terminal portion of the PB1-F2 protein binds to MAVS in a region that contains the transmembrane domain. Strikingly, PB1-F2 66S was observed to bind to MAVS more efficiently than PB1-F2 66N. We also tested the effect of PB1-F2 on the IFN antagonist functions of the polymerase proteins PB1, PB2, and PA and observed enhanced IFN inhibition by the PB1 and PB2 proteins in combination with PB1-F2 but not by the PA protein. Using a flow cytometry-based assay, we demonstrate that the PB1-F2 protein inhibits MAVS-mediated IFN synthesis by decreasing the mitochondrial membrane potential (MMP). Interestingly, PB1-F2 66S affected the MMP more efficiently than wild-type PB1-F2. In summary, the results of our study identify the molecular mechanism by which the influenza virus PB1-F2 N66S protein increases virulence.
Details
- Title: Subtitle
- Influenza Virus Protein PB1-F2 Inhibits the Induction of Type I Interferon by Binding to MAVS and Decreasing Mitochondrial Membrane Potential
- Creators
- Zsuzsanna T Varga - Department of MicrobiologyAlesha Grant - Department of MicrobiologyBalaji Manicassamy - Department of MicrobiologyPeter Palese - Department of Microbiology
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.86(16), pp.8359-8366
- Publisher
- American Society for Microbiology
- DOI
- 10.1128/JVI.01122-12
- PMID
- 22674996
- PMCID
- PMC3421771
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Language
- English
- Date published
- 08/2012
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984083266302771
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