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Article: Amino Acid Substitutions in Polymerase Basic Protein 2 Gene Contribute to the Pathogenicity of the Novel A/H7N9 Influenza Virus in Mammalian Hosts

TitleAmino Acid Substitutions in Polymerase Basic Protein 2 Gene Contribute to the Pathogenicity of the Novel A/H7N9 Influenza Virus in Mammalian Hosts
Authors
Issue Date2014
PublisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/
Citation
Journal of Virology, 2014, v. 88 n. 6, p. 3568-3576 How to Cite?
AbstractA novel avian-origin influenza A/H7N9 virus emerged in 2013 to cause more than 130 cases of zoonotic human disease, with an overall case fatality rate of around 30% in cases detected. It has been shown that an E-to-K amino acid change at residue 627 of polymerase basic protein 2 (PB2) occurred frequently in the H7N9 isolates obtained from humans but not in viruses isolated from poultry. Although this mutation has been reported to confer increased mammalian pathogenicity in other avian influenza subtypes, it has not been experimentally investigated in the H7N9 virus. In this study, we determined the contribution of PB2-E627K in H7N9 virus to its pathogenicity in mammalian hosts. In addition, the compensatory role of the PB2 mutations T271A, Q591K, and D701N in H7N9 virus was investigated. We characterized the activity of polymerase complexes with these PB2 mutations and found that they enhance the polymerase activity in human 293T cells. The rescued mutants enhanced growth in mammalian cells in vitro. Mice infected with the H7N9 mutant containing the avian signature protein PB2-627E showed a marked decrease in disease severity (weight loss) and pathology compared to mice infected with the wild-type strain (PB2-627K) or other PB2 mutants. Also, mutants with PB2-627E showed lower virus replication and proinflammatory cytokine responses in the lungs of the virus-infected mice, which may contribute to pathogenicity. Our results suggest that these amino acid substitutions contribute to mouse pathogenicity and mammalian adaptation.
Persistent Identifierhttp://hdl.handle.net/10722/195756
ISSN
2015 Impact Factor: 4.606
2015 SCImago Journal Rankings: 3.347
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorMok, KPen_US
dc.contributor.authorLee, HYHen_US
dc.contributor.authorLestra, Men_US
dc.contributor.authorNicholls, JMen_US
dc.contributor.authorChan, MCWen_US
dc.contributor.authorSia, SFen_US
dc.contributor.authorZhu, Hen_US
dc.contributor.authorPoon, LLMen_US
dc.contributor.authorGuan, Yen_US
dc.contributor.authorPeiris, JSMen_US
dc.date.accessioned2014-03-07T04:35:12Z-
dc.date.available2014-03-07T04:35:12Z-
dc.date.issued2014en_US
dc.identifier.citationJournal of Virology, 2014, v. 88 n. 6, p. 3568-3576en_US
dc.identifier.issn0022-538X-
dc.identifier.urihttp://hdl.handle.net/10722/195756-
dc.description.abstractA novel avian-origin influenza A/H7N9 virus emerged in 2013 to cause more than 130 cases of zoonotic human disease, with an overall case fatality rate of around 30% in cases detected. It has been shown that an E-to-K amino acid change at residue 627 of polymerase basic protein 2 (PB2) occurred frequently in the H7N9 isolates obtained from humans but not in viruses isolated from poultry. Although this mutation has been reported to confer increased mammalian pathogenicity in other avian influenza subtypes, it has not been experimentally investigated in the H7N9 virus. In this study, we determined the contribution of PB2-E627K in H7N9 virus to its pathogenicity in mammalian hosts. In addition, the compensatory role of the PB2 mutations T271A, Q591K, and D701N in H7N9 virus was investigated. We characterized the activity of polymerase complexes with these PB2 mutations and found that they enhance the polymerase activity in human 293T cells. The rescued mutants enhanced growth in mammalian cells in vitro. Mice infected with the H7N9 mutant containing the avian signature protein PB2-627E showed a marked decrease in disease severity (weight loss) and pathology compared to mice infected with the wild-type strain (PB2-627K) or other PB2 mutants. Also, mutants with PB2-627E showed lower virus replication and proinflammatory cytokine responses in the lungs of the virus-infected mice, which may contribute to pathogenicity. Our results suggest that these amino acid substitutions contribute to mouse pathogenicity and mammalian adaptation.en_US
dc.languageengen_US
dc.publisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/-
dc.relation.ispartofJournal of Virologyen_US
dc.titleAmino Acid Substitutions in Polymerase Basic Protein 2 Gene Contribute to the Pathogenicity of the Novel A/H7N9 Influenza Virus in Mammalian Hostsen_US
dc.typeArticleen_US
dc.identifier.emailMok, KP: ch02mkp@hkucc.hku.hken_US
dc.identifier.emailLee, HYH: horlee@hkucc.hku.hken_US
dc.identifier.emailNicholls, JM: jmnichol@hkucc.hku.hken_US
dc.identifier.emailChan, MCW: mchan@hku.hken_US
dc.identifier.emailSia, SF: sfsia@hkucc.hku.hken_US
dc.identifier.emailZhu, H: zhuhch@hku.hken_US
dc.identifier.emailPoon, LLM: llmpoon@hkucc.hku.hken_US
dc.identifier.emailGuan, Y: yguan@hkucc.hku.hken_US
dc.identifier.emailPeiris, JSM: malik@hkucc.hku.hken_US
dc.identifier.authorityMok, KP=rp01805en_US
dc.identifier.authorityNicholls, JM=rp00364en_US
dc.identifier.authorityChan, MCW=rp00420en_US
dc.identifier.authorityZhu, H=rp01535en_US
dc.identifier.authorityPoon, LLM=rp00484en_US
dc.identifier.authorityGuan, Y=rp00397en_US
dc.identifier.authorityPeiris, JSM=rp00410en_US
dc.identifier.doi10.1128/JVI.02740-13en_US
dc.identifier.pmid24403592-
dc.identifier.hkuros228195en_US
dc.identifier.volume88en_US
dc.identifier.issue6en_US
dc.identifier.spage3568en_US
dc.identifier.epage3576en_US
dc.identifier.isiWOS:000332126000046-
dc.publisher.placeUnited States-

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