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A complicated message: identification of a novel PB1-related protein translated from influenza A virus segment 2 mRNA
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Wise, Helen M., Foeglein, Agnes, Sun, Jiechao, Dalton, Rosa Maria, Patel, Sheetal, Howard, Wendy, Anderson, Emma C., Barclay, Wendy S. and Digard, Paul (2009) A complicated message: identification of a novel PB1-related protein translated from influenza A virus segment 2 mRNA. Journal of Virology, Vol.83 (No.16). pp. 8021-8031. doi:10.1128/JVI.00826-09 ISSN 0022-538X.
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Official URL: http://dx.doi.org/10.1128/JVI.00826-09
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.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Subjects: | Q Science > QR Microbiology > QR355 Virology | ||||
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) > Biological Sciences ( -2010) | ||||
| Journal or Publication Title: | Journal of Virology | ||||
| Publisher: | American Society for Microbiology | ||||
| ISSN: | 0022-538X | ||||
| Official Date: | 15 August 2009 | ||||
| Dates: |
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| Volume: | Vol.83 | ||||
| Number: | No.16 | ||||
| Number of Pages: | 11 | ||||
| Page Range: | pp. 8021-8031 | ||||
| DOI: | 10.1128/JVI.00826-09 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
| Funder: | Medical Research Council, Wellcome Trust | ||||
| Grant number: | G0700815 |
Data sourced from Thomson Reuters' Web of Knowledge
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