title: The influenza A virus protein PB1-F2: killing two birds with one stone?
abstract: 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. The PB1-F2 protein has been shown to contribute to viral pathogenicity, but the molecular mechanisms for mediating virulence have been unclear. Previous reports demonstrate that PB1-F2 promotes cell death, causes immunopathology and increases pro-inflammatory responses. Our group has identified a single point mutation from asparagine (N) to serine (S) at position 66 in the PB1-F2 protein that dramatically increases the virulence of highly pathogenic avian H5N1 influenza viruses and of the 1918 pandemic strain. In search for the mechanism by which PB1-F2 N66S increases pathogenicity, we have identified and characterized a novel function of PB1-F2, i.e. interferon antagonism, both in vitro and in the mouse model. Here, we discuss a hypothesis for a possible molecular link between the pro-apoptotic and anti-interferon functions of PB1-F2.
authors.affiliation: Department of Microbiology, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Zsuzsanna T
authors.initials: ZT
authors.lastname: Varga
authors.forename: Peter
authors.initials: P
authors.lastname: Palese
mesh_terms: D017209:Apoptosis; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D007251:Influenza, Human / Q000276:immunology / Q000503:physiopathology / Q000821:virology*; D007372:Interferons / Q000037:antagonists & inhibitors* / Q000276:immunology; D020125:Mutation, Missense; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*; D014774:Virulence
chemical_list: C442816:PB1-F2 protein, Influenza A virus; D014764:Viral Proteins; D007372:Interferons