title: Influenza A virus PB1-F2 protein expression is regulated in a strain-specific manner by sequences located downstream of the PB1-F2 initiation codon.
abstract: Translation of influenza A virus PB1-F2 occurs in a second open reading frame (ORF) of the PB1 gene segment. PB1-F2 has been implicated in regulation of polymerase activity, immunopathology, susceptibility to secondary bacterial infection, and induction of apoptosis. Experimental evidence of PB1-F2 molecular function during infection has been collected primarily from human and avian viral isolates. As the 2009 H1N1 (H1N1pdm09) strain highlighted, some swine-derived influenza viruses have the capacity to infect human hosts and emerge as a pandemic. Understanding the impact that virulence factors from swine isolates have on both human and swine health could aid in early identification of viruses with pandemic potential. Studies examining PB1-F2 from swine isolates have focused primarily on H1N1pdm09, which does not encode PB1-F2 but was engineered to carry a full-length PB1-F2 ORF to assess the impact on viral replication and pathogenicity. However, experimental evidence of PB1-F2 protein expression from swine lineage viruses has not been demonstrated. Here, we reveal that during infection, PB1-F2 expression levels are substantially different in swine and human influenza viruses. We provide evidence that PB1-F2 expression is regulated at the translational level, with very low levels of PB1-F2 expression from swine lineage viruses relative to a human isolate PB1-F2. Translational regulation of PB1-F2 expression was partially mapped to two independent regions within the PB1 mRNA, located downstream of the PB1-F2 start site. Our data suggest that carrying a full-length PB1-F2 ORF may not be predictive of PB1-F2 expression in infected cells for all influenza A viruses.
authors.affiliation: Department of Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Buehler
authors.forename: Deepak
authors.initials: D
authors.lastname: Navi
authors.forename: Alessio
authors.initials: A
authors.lastname: Lorusso
authors.forename: Amy
authors.initials: A
authors.lastname: Vincent
authors.forename: Kelly
authors.initials: K
authors.lastname: Lager
authors.forename: Cathy L
authors.initials: CL
authors.lastname: Miller
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002642:Chick Embryo; D018387:Codon, Initiator / Q000235:genetics*; D004285:Dogs; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000821:virology; D015967:Gene Expression Regulation, Viral; D006801:Humans; D047468:Immunoprecipitation; D053118:Influenza A Virus, H1N1 Subtype / Q000145:classification / Q000302:isolation & purification / Q000502:physiology*; D007668:Kidney / Q000166:cytology / Q000378:metabolism / Q000821:virology; D008856:Microscopy, Fluorescence; D009976:Orthomyxoviridae Infections / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D010802:Phylogeny; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication
chemical_list: D018387:Codon, Initiator; C442816:PB1-F2 protein, Influenza A virus; D012333:RNA, Messenger; D014764:Viral Proteins