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Article: Amino acid substitutions V63I or A37S/I61T/V63I/V100A in the PA N-terminal domain increase the virulence of H7N7 influenza A virus

TitleAmino acid substitutions V63I or A37S/I61T/V63I/V100A in the PA N-terminal domain increase the virulence of H7N7 influenza A virus
Authors
Issue Date2016
PublisherNature Publishing Group: Open Access Journals. The Journal's web site is located at http://www.nature.com/srep/index.html
Citation
Scientific Reports, 2016, v. 6, article no. 37800, p. 1-11 How to Cite?
AbstractThe PA N-terminal domain (PA-Nter) is essential for viral transcription and replication. Here we identified PA-Nter substitutions A37S, I61T, V63I and V100A in recently emerged avian influenza A viruses (IAVs) with potential effect on virus pathogenicity and/or host adaptation. We introduced the identified PA-Nter substitutions into avian H7N7 IAV by reverse genetics. Our results showed that single substitution V63I and combined substitutions, I61T/V63I and A37S/I61T/V63I/V100A (Mfour), significantly increased virus growth capacity in mammalian cells. Meanwhile, these substitutions conferred higher virus transcription/replication capacity by producing more mRNA, cRNA and vRNA. Consistently, the polymerase activity and the endonuclease activity were enhanced by these PA-Nter substitutions. Notably, substitutions V63I and Mfour strongly increased virus replication and virulence in mice. Collectively, our findings demonstrated that the PA-Nter substitutions V63I and Mfour enhanced IAV pathogenicity through modification of the polymerase activity and the endonuclease activity, which added to the evolving knowledge of IAV virulence determinants.
Persistent Identifierhttp://hdl.handle.net/10722/238680
ISSN
2017 Impact Factor: 4.122
2015 SCImago Journal Rankings: 2.073
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHu, M-
dc.contributor.authorChu, H-
dc.contributor.authorZhang, K-
dc.contributor.authorSingh, K-
dc.contributor.authorLi, C-
dc.contributor.authorYuan, S-
dc.contributor.authorChow, BKC-
dc.contributor.authorSong, W-
dc.contributor.authorZhou, J-
dc.contributor.authorZheng, B-
dc.date.accessioned2017-02-20T01:24:41Z-
dc.date.available2017-02-20T01:24:41Z-
dc.date.issued2016-
dc.identifier.citationScientific Reports, 2016, v. 6, article no. 37800, p. 1-11-
dc.identifier.issn2045-2322-
dc.identifier.urihttp://hdl.handle.net/10722/238680-
dc.description.abstractThe PA N-terminal domain (PA-Nter) is essential for viral transcription and replication. Here we identified PA-Nter substitutions A37S, I61T, V63I and V100A in recently emerged avian influenza A viruses (IAVs) with potential effect on virus pathogenicity and/or host adaptation. We introduced the identified PA-Nter substitutions into avian H7N7 IAV by reverse genetics. Our results showed that single substitution V63I and combined substitutions, I61T/V63I and A37S/I61T/V63I/V100A (Mfour), significantly increased virus growth capacity in mammalian cells. Meanwhile, these substitutions conferred higher virus transcription/replication capacity by producing more mRNA, cRNA and vRNA. Consistently, the polymerase activity and the endonuclease activity were enhanced by these PA-Nter substitutions. Notably, substitutions V63I and Mfour strongly increased virus replication and virulence in mice. Collectively, our findings demonstrated that the PA-Nter substitutions V63I and Mfour enhanced IAV pathogenicity through modification of the polymerase activity and the endonuclease activity, which added to the evolving knowledge of IAV virulence determinants.-
dc.languageeng-
dc.publisherNature Publishing Group: Open Access Journals. The Journal's web site is located at http://www.nature.com/srep/index.html-
dc.relation.ispartofScientific Reports-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleAmino acid substitutions V63I or A37S/I61T/V63I/V100A in the PA N-terminal domain increase the virulence of H7N7 influenza A virus-
dc.typeArticle-
dc.identifier.emailChu, H: hinchu@hku.hk-
dc.identifier.emailZhang, K: kezhang1@hku.hk-
dc.identifier.emailLi, C: licun@hku.hk-
dc.identifier.emailYuan, S: yuansf@hku.hk-
dc.identifier.emailChow, BKC: bkcc@hku.hk-
dc.identifier.emailSong, W: wjsong@hkucc.hku.hk-
dc.identifier.emailZhou, J: jiezhou@hku.hk-
dc.identifier.emailZheng, B: bzheng@hkucc.hku.hk-
dc.identifier.authorityChu, H=rp02125-
dc.identifier.authorityChow, BKC=rp00681-
dc.identifier.authorityZhou, J=rp01412-
dc.identifier.authorityZheng, B=rp00353-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/srep37800-
dc.identifier.pmid27886255-
dc.identifier.pmcidPMC5122915-
dc.identifier.scopuseid_2-s2.0-84998787328-
dc.identifier.hkuros271252-
dc.identifier.volume6-
dc.identifier.spagearticle no. 37800, p. 1-
dc.identifier.epagearticle no. 37800, p. 11-
dc.identifier.isiWOS:000388558900003-
dc.publisher.placeUnited Kingdom-

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