Naturally occurring mutations in the PA gene are key contributors to increased virulence of pandemic H1N1/09 influenza virus in mice

Sun, Y. and Xu, Q. and Shen, Y. and Liu, L. and Wei, K. and Sun, H. and Pu, J. and Chang, K.-C. and Liu, J. (2014) Naturally occurring mutations in the PA gene are key contributors to increased virulence of pandemic H1N1/09 influenza virus in mice. Journal of Virology, 88 (8). pp. 4600-4604. ISSN 0022-538X

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Abstract

We examined the molecular basis of virulence of pandemic H1N1/09 influenza viruses by reverse genetics based on two H1N1/09 virus isolates (A/California/04/2009 [CA04] and A/swine/Shandong/731/2009 [SD731]) with contrasting pathogenicities in mice. We found that four amino acid mutations (P224S in the PA protein [PA-P224S], PB2-T588I, NA-V106I, and NS1-I123V) contributed to the lethal phenotype of SD731. In particular, the PA-P224S mutation when combined with PA-A70V in CA04 drastically reduced the virus's 50% mouse lethal dose (LD50), by almost 1,000-fold.

Item Type: Article
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Veterinary Medicine and Science
Identification Number: 10.1128/JVI.03158-13
Depositing User: Eprints, Support
Date Deposited: 30 Jun 2017 14:06
Last Modified: 12 Oct 2017 22:58
URI: http://eprints.nottingham.ac.uk/id/eprint/43920

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