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Journal of Virology, August 2009, p. 8021-8031, Vol. 83, No. 16
0022-538X/09/$08.00+0     doi:10.1128/JVI.00826-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

A Complicated Message: Identification of a Novel PB1-Related Protein Translated from Influenza A Virus Segment 2 mRNA{triangledown}

Helen M. Wise,1 Agnes Foeglein,1 Jiechao Sun,1 Rosa Maria Dalton,1 Sheetal Patel,1 Wendy Howard,2 Emma C. Anderson,3 Wendy S. Barclay,2 and Paul Digard1*

Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom,1 Department of Virology, Faculty of Medicine, Imperial College London, Norfolk Place, London W2 1PG, United Kingdom,2 Department of Biological Sciences, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, United Kingdom3

Received 23 April 2009/ Accepted 29 May 2009

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.

* Corresponding author. Mailing address: Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom. Phone: 44 1223 336920. Fax: 44 1223 336926. E-mail: pd1{at}mole.bio.cam.ac.uk

{triangledown} Published ahead of print on 3 June 2009.

Journal of Virology, August 2009, p. 8021-8031, Vol. 83, No. 16
0022-538X/09/$08.00+0     doi:10.1128/JVI.00826-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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