title: A complicated message: Identification of a novel PB1-related protein translated from influenza A virus segment 2 mRNA.
abstract: Influenza A virus segment 2 is known to encode two polypeptides in overlapping open reading frames: PB1, the polymerase, and PB1-F2, a proapoptotic virulence factor. We show that a third major polypeptide is synthesized from PB1 mRNA via differential AUG codon usage. PB1 codon 40 directs translation of an N-terminally truncated version of the polypeptide (N40) that lacks transcriptase function but nevertheless interacts with PB2 and the polymerase complex in the cellular environment. Importantly, the expression of N40, PB1-F2, and PB1 are interdependent, and certain mutations previously used to ablate PB1-F2 production affected N40 accumulation. Removal of the PB1-F2 AUG upregulated N40 synthesis, while truncating PB1-F2 after codon 8 (with a concomitant M40I change in PB1) abolished N40 expression. A virus lacking both N40 and PB1-F2 replicated normally. However, viruses that did not express N40 but retained an intact PB1-F2 gene overexpressed PB1 early in infection and replicated slowly in tissue culture. Thus, the influenza A virus proteome includes a 12th primary translation product that (similarly to PB1-F2) is nonessential for virus viability but whose loss, in particular genetic backgrounds, is detrimental to virus replication.
authors.affiliation: Department of Pathology, University of Cambridge, United Kingdom.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Wise
authors.forename: Agnes
authors.initials: A
authors.lastname: Foeglein
authors.forename: Jiechao
authors.initials: J
authors.lastname: Sun
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Dalton
authors.forename: Sheetal
authors.initials: S
authors.lastname: Patel
authors.forename: Wendy
authors.initials: W
authors.lastname: Howard
authors.forename: Emma C
authors.initials: EC
authors.lastname: Anderson
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Barclay
authors.forename: Paul
authors.initials: P
authors.lastname: Digard
mesh_terms: D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000502:physiology*; D010446:Peptide Fragments / Q000235:genetics* / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication
chemical_list: D010446:Peptide Fragments; D010455:Peptides; D012333:RNA, Messenger; D012367:RNA, Viral; D014764:Viral Proteins; C077346:influenza virus polymerase basic protein 1