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Naturally Occurring Mutations in the PA Gene Are Key Contributors to Increased Virulence of Pandemic H1N1/09 Influenza Virus in Mice

Sun, Y.; Xu, Q.; Shen, Y.; Liu, L.; Wei, K.; Sun, H.; Pu, J.; Chang, K.-C.; Liu, J.

Authors

Y. Sun

Q. Xu

Y. Shen

L. Liu

K. Wei

H. Sun

J. Pu

K.-C. Chang

J. Liu



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.

Journal Article Type Article
Publication Date Apr 15, 2014
Journal Journal of Virology
Print ISSN 0022-538X
Electronic ISSN 0022-538X
Publisher American Society for Microbiology
Peer Reviewed Peer Reviewed
Volume 88
Issue 8
Pages 4600-4604
APA6 Citation Sun, Y., Xu, Q., Shen, Y., Liu, L., Wei, K., Sun, H., …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), 4600-4604. https://doi.org/10.1128/jvi.03158-13
DOI https://doi.org/10.1128/jvi.03158-13
Publisher URL http://jvi.asm.org/content/88/8/4600
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf
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