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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

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.

Citation

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

Journal Article Type Article
Acceptance Date Feb 3, 2014
Online Publication Date Mar 26, 2014
Publication Date Apr 15, 2014
Deposit Date Jun 30, 2017
Journal Journal of Virology
Print ISSN 0022-538X
Electronic ISSN 1098-5514
Publisher American Society for Microbiology
Peer Reviewed Peer Reviewed
Volume 88
Issue 8
Pages 4600-4604
DOI https://doi.org/10.1128/jvi.03158-13
Public URL https://nottingham-repository.worktribe.com/output/731501
Publisher URL http://jvi.asm.org/content/88/8/4600