Giuseppe
Emeritus
J Virol. 2009 Jun 3. [Epub ahead of print]
A complicated message: identification of a novel PB1-related protein translated from influenza A segment 2 mRNA.
Wise HM, Foeglein A, Sun J, Dalton RM, Patel S, Howard W, Anderson EC, Barclay WS, Digard P. Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, CB2 1QP, UK; Department of Virology, Faculty of Medicine, Imperial College London, Norfolk Place, London, W2 1PG, UK; and Department of Biological Sciences, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK.
Influenza A virus segment 2 is known to encode two polypeptides in overlapping ORFs: PB1, the polymerase, and PB1-F2, a proapoptotic virulence factor. We show that a third major polypeptide is synthesised 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, 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 over-expressed PB1 early in infection and replicated slowly in tissue culture.
Thus the influenza A virus proteome includes a twelfth primary translation product that (similarly to PB1-F2) is non-essential for virus viability but whose loss, in particular genetic backgrounds, is detrimental to virus replication.
PMID: 19494001 [PubMed - as supplied by publishe
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A complicated message: identification of a novel PB1-related protein translated from influenza A segment 2 mRNA.
Wise HM, Foeglein A, Sun J, Dalton RM, Patel S, Howard W, Anderson EC, Barclay WS, Digard P. Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, CB2 1QP, UK; Department of Virology, Faculty of Medicine, Imperial College London, Norfolk Place, London, W2 1PG, UK; and Department of Biological Sciences, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK.
Influenza A virus segment 2 is known to encode two polypeptides in overlapping ORFs: PB1, the polymerase, and PB1-F2, a proapoptotic virulence factor. We show that a third major polypeptide is synthesised 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, 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 over-expressed PB1 early in infection and replicated slowly in tissue culture.
Thus the influenza A virus proteome includes a twelfth primary translation product that (similarly to PB1-F2) is non-essential for virus viability but whose loss, in particular genetic backgrounds, is detrimental to virus replication.
PMID: 19494001 [PubMed - as supplied by publishe
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