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.

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