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Article: Evaluation of the human adaptation of influenza A/H7N9 virus in PB2 protein using human and swine respiratory tract explant cultures

TitleEvaluation of the human adaptation of influenza A/H7N9 virus in PB2 protein using human and swine respiratory tract explant cultures
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, p. 35401:1-11 How to Cite?
AbstractNovel avian H7N9 virus emerged in China in 2013 resulting in a case fatality rate of around 39% and continues to pose zoonotic and pandemic risk. Amino acid substitutions in PB2 protein were shown to influence the pathogenicity and transmissibility of H7N9 following experimental infection of ferrets and mice. In this study, we evaluated the role of amino acid substitution PB2-627K or compensatory changes at PB2-591K and PB2-701N, on the tropism and replication competence of H7N9 viruses for human and swine respiratory tracts using ex vivo organ explant cultures. Recombinant viruses of A/Shanghai/2/2013 (rgH7N9) and its mutants with PB2-K627E, PB2-K627E + Q591K and PB2-K627E + D701N were generated by plasmid-based reverse genetics. PB2-E627K was essential for efficient replication of rgH7N9 in ex vivo cultures of human and swine respiratory tracts. Mutant rgPB2-K627E + D701N replicated better than rgPB2-K627E in human lung but not as well as rgH7N9 virus. The rgPB2-K627E mutant failed to replicate in human type I-like pneumocytes (ATI) and peripheral blood monocyte-derived macrophages (PMϕ) at 37 °C while the compensatory mutant rgPB2-K627E + Q591K and rgPB2-K627E + D701N had partly restored replication competence in PMϕ. Our results demonstrate that PB2-E627K was important for efficient replication of influenza H7N9 in both human and swine respiratory tracts.
Persistent Identifierhttp://hdl.handle.net/10722/236523
ISSN
2017 Impact Factor: 4.122
2015 SCImago Journal Rankings: 2.073
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChan, LY-
dc.contributor.authorBUI, HT-
dc.contributor.authorMok, KP-
dc.contributor.authorNg, MMT-
dc.contributor.authorNicholls, JM-
dc.contributor.authorPeiris, JSM-
dc.contributor.authorChan, MCW-
dc.contributor.authorChan, WY-
dc.date.accessioned2016-11-25T00:54:35Z-
dc.date.available2016-11-25T00:54:35Z-
dc.date.issued2016-
dc.identifier.citationScientific Reports, 2016, v. 6, p. 35401:1-11-
dc.identifier.issn2045-2322-
dc.identifier.urihttp://hdl.handle.net/10722/236523-
dc.description.abstractNovel avian H7N9 virus emerged in China in 2013 resulting in a case fatality rate of around 39% and continues to pose zoonotic and pandemic risk. Amino acid substitutions in PB2 protein were shown to influence the pathogenicity and transmissibility of H7N9 following experimental infection of ferrets and mice. In this study, we evaluated the role of amino acid substitution PB2-627K or compensatory changes at PB2-591K and PB2-701N, on the tropism and replication competence of H7N9 viruses for human and swine respiratory tracts using ex vivo organ explant cultures. Recombinant viruses of A/Shanghai/2/2013 (rgH7N9) and its mutants with PB2-K627E, PB2-K627E + Q591K and PB2-K627E + D701N were generated by plasmid-based reverse genetics. PB2-E627K was essential for efficient replication of rgH7N9 in ex vivo cultures of human and swine respiratory tracts. Mutant rgPB2-K627E + D701N replicated better than rgPB2-K627E in human lung but not as well as rgH7N9 virus. The rgPB2-K627E mutant failed to replicate in human type I-like pneumocytes (ATI) and peripheral blood monocyte-derived macrophages (PMϕ) at 37 °C while the compensatory mutant rgPB2-K627E + Q591K and rgPB2-K627E + D701N had partly restored replication competence in PMϕ. Our results demonstrate that PB2-E627K was important for efficient replication of influenza H7N9 in both human and swine respiratory tracts.-
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.titleEvaluation of the human adaptation of influenza A/H7N9 virus in PB2 protein using human and swine respiratory tract explant cultures-
dc.typeArticle-
dc.identifier.emailChan, LY: louisa12@hku.hk-
dc.identifier.emailMok, KP: ch02mkp@hkucc.hku.hk-
dc.identifier.emailNg, MMT: mmtng@hku.hk-
dc.identifier.emailNicholls, JM: jmnichol@hkucc.hku.hk-
dc.identifier.emailPeiris, JSM: malik@hkucc.hku.hk-
dc.identifier.emailChan, MCW: mchan@hku.hk-
dc.identifier.emailChan, WY: reneewy@hku.hk-
dc.identifier.authorityMok, KP=rp01805-
dc.identifier.authorityNicholls, JM=rp00364-
dc.identifier.authorityPeiris, JSM=rp00410-
dc.identifier.authorityChan, MCW=rp00420-
dc.identifier.authorityChan, WY=rp01596-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/srep35401-
dc.identifier.hkuros270631-
dc.identifier.volume6-
dc.identifier.spage35401:1-
dc.identifier.epage11-
dc.identifier.isiWOS:000385306400001-
dc.publisher.placeUnited Kingdom-

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