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., …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: 0022-538X
• 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