Tauber, S., Ligertwood, Y., Quigg-Nicol, M., Dutia, B.M. and Elliott, R.M. (2012) Behaviour of influenza A viruses differentially expressing segment 2 gene products in vitro and in vivo. Journal of General Virology, 93(4), pp. 840-849. (doi: 10.1099/vir.0.039966-0)
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Abstract
The influenza A virus genome comprises eight segments of negative-sense RNA that encode up to 12 proteins. RNA segment 2 encodes three proteins, PB1, PB1-F2 and N40, that are translated from the same mRNA by ribosomal leaky scanning and reinitiation. PB1 is a subunit of the trimeric viral RNA polymerase. PB1-F2 has been reported to be a potential virulence factor, and has been shown to be involved in a number of activities including induction of apoptosis, regulation of virus replication and modulation of the immune response. No function has yet been ascribed to N40, which represents an N-terminally deleted form of PB1. Previous studies on PB1-F2 function mainly used viruses genetically engineered to prevent PB1-F2 expression by mutation of the PB1-F2 start codon. However, ablation of the start codon was shown to increase the expression level of the downstream protein N40. In the present study, we generated recombinant A/WSN/33 viruses carrying different combinations of PB1-F2- and N40-knockout mutations. Overexpression of N40 in a PB1-F2-deficient background had a detrimental effect on virus growth <i>in vitro</i> and <i>in vivo</i>. However, ablation of PB1-F2 or N40 expression individually was not disadvantageous for the virus. Primer-extension analyses revealed an increase in vRNA production by viruses that overexpressed N40. Our data suggest that the observed attenuation of mutant viruses <i>in vitro</i> and <i>in vivo</i> results from these changes in transcription and replication.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Elliott, Professor Richard |
| Authors: | Tauber, S., Ligertwood, Y., Quigg-Nicol, M., Dutia, B.M., and Elliott, R.M. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Journal of General Virology |
| ISSN: | 0022-1317 |
| ISSN (Online): | 1465-2099 |
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