Naturally occurring mutations in the PA gene are key contributors to increased virulence of pandemic H1N1/09 influenza virus in mice
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 t...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
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American Society for Microbiology
2014
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| Online Access: | https://eprints.nottingham.ac.uk/43920/ |
| _version_ | 1848796796483010560 |
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| author | Sun, Y. Xu, Q. Shen, Y. Liu, L. Wei, K. Sun, H. Pu, J. Chang, K.-C. Liu, J. |
| author_facet | Sun, Y. Xu, Q. Shen, Y. Liu, L. Wei, K. Sun, H. Pu, J. Chang, K.-C. Liu, J. |
| author_sort | Sun, Y. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:53:41Z |
| format | Article |
| id | nottingham-43920 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:53:41Z |
| publishDate | 2014 |
| publisher | American Society for Microbiology |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-439202020-05-04T16:50:09Z https://eprints.nottingham.ac.uk/43920/ 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. 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. American Society for Microbiology 2014-08-01 Article PeerReviewed Sun, Y., Xu, Q., Shen, Y., Liu, L., Wei, K., Sun, H., Pu, J., 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 http://jvi.asm.org/content/88/8/4600 doi:10.1128/JVI.03158-13 doi:10.1128/JVI.03158-13 |
| spellingShingle | Sun, Y. Xu, Q. Shen, Y. Liu, L. Wei, K. Sun, H. Pu, J. Chang, K.-C. Liu, J. Naturally occurring mutations in the PA gene are key contributors to increased virulence of pandemic H1N1/09 influenza virus in mice |
| title | Naturally occurring mutations in the PA gene are key contributors to increased virulence of pandemic H1N1/09 influenza virus in mice |
| title_full | Naturally occurring mutations in the PA gene are key contributors to increased virulence of pandemic H1N1/09 influenza virus in mice |
| title_fullStr | Naturally occurring mutations in the PA gene are key contributors to increased virulence of pandemic H1N1/09 influenza virus in mice |
| title_full_unstemmed | Naturally occurring mutations in the PA gene are key contributors to increased virulence of pandemic H1N1/09 influenza virus in mice |
| title_short | Naturally occurring mutations in the PA gene are key contributors to increased virulence of pandemic H1N1/09 influenza virus in mice |
| title_sort | naturally occurring mutations in the pa gene are key contributors to increased virulence of pandemic h1n1/09 influenza virus in mice |
| url | https://eprints.nottingham.ac.uk/43920/ https://eprints.nottingham.ac.uk/43920/ https://eprints.nottingham.ac.uk/43920/ |