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...

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Main Authors: Sun, Y., Xu, Q., Shen, Y., Liu, L., Wei, K., Sun, H., Pu, J., Chang, K.-C., Liu, J.
Format: Article
Published: American Society for Microbiology 2014
Online Access:https://eprints.nottingham.ac.uk/43920/
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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.
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publishDate 2014
publisher American Society for Microbiology
recordtype eprints
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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/