The influenza virus protein PB1-F2 inhibits the induction of type i interferon at the level of the MAVS adaptor protein

Pb1-f2 is a 90 amino acid protein that is expressed from the +1 open reading frame in the pb1 gene of some influenza a viruses and has been shown to contribute to viral pathogenicity. notably,a serine at position 66 (66s) in pb1-f2 is known to increase virulence compared to an isogenic virus with an asparagine (66n) at this position. recently,we found that an influenza virus expressing pb1-f2 n66s suppresses interferon (ifn)-stimulated genes in mice. to characterize this phenomenon,we employed several in vitro assays. overexpression of the a/puerto rico/8/1934 (pr8) pb1-f2 protein in 293t cells decreased rig-i mediated activation of an ifn-β reporter and secretion of ifn as determined by bioassay. of note,the pb1-f2 n66s protein showed enhanced ifn antagonism activity compared to pb1-f2 wildtype. similar observations were found in the context of viral infection with a pr8 pb1-f2 n66s virus. to understand the relationship between ns1,a previously described influenza virus protein involved in suppression of ifn synthesis,and pb1-f2,we investigated the induction of ifn when ns1 and pb1-f2 were co-expressed in an in vitro transfection system. in this assay we found that pb1-f2 n66s further reduced ifn induction in the presence of ns1. by inducing the ifn-β reporter at different levels in the signaling cascade,we found that pb1-f2 inhibited ifn production at the level of the mitochondrial antiviral signaling protein (mavs). furthermore,immunofluorescence studies revealed that pb1-f2 co-localizes with mavs. in summary,we have characterized the anti-interferon function of pb1-f2 and we suggest that this activity contributes to the enhanced pathogenicity seen with pb1-f2 n66s- expressing influenza viruses. © 2011 varga et al.