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Article: Preventing an Antigenically Disruptive Mutation in Egg-Based H3N2 Seasonal Influenza Vaccines by Mutational Incompatibility

TitlePreventing an Antigenically Disruptive Mutation in Egg-Based H3N2 Seasonal Influenza Vaccines by Mutational Incompatibility
Authors
KeywordsAntigenicity
Egg-adaptive mutation
Epistasis
Hemagglutinin
Influenza virus
Receptor binding
Vaccine
Issue Date2019
PublisherCell Press. The Journal's web site is located at http://www.cellhostandmicrobe.com
Citation
Cell Host & Microbe, 2019, v. 25 n. 6, p. 836-844.e5 How to Cite?
AbstractEgg-based seasonal influenza vaccines are the major preventive countermeasure against influenza virus. However, their effectiveness can be compromised when antigenic changes arise from egg-adaptive mutations on influenza hemagglutinin (HA). The L194P mutation is commonly observed in egg-based H3N2 vaccine seed strains and significantly alters HA antigenicity. An approach to prevent L194P would therefore be beneficial. We show that emergence of L194P during egg passaging can be impeded by preexistence of a G186V mutation, revealing strong incompatibility between these mutations. X-ray structures illustrate that individual G186V and L194P mutations have opposing effects on the HA receptor-binding site (RBS), and when both G186V and L194P are present, the RBS is severely disrupted. Importantly, wild-type HA antigenicity is maintained with G186V, but not L194P. Our results demonstrate that these epistatic interactions can be used to prevent the emergence of mutations that adversely alter antigenicity during egg adaptation.
Persistent Identifierhttp://hdl.handle.net/10722/272081
ISSN
2017 Impact Factor: 17.872
2015 SCImago Journal Rankings: 8.283
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWu, NC-
dc.contributor.authorLv, H-
dc.contributor.authorThompson, AJ-
dc.contributor.authorWu, DC-
dc.contributor.authorNg, WWS-
dc.contributor.authorKadam, RU-
dc.contributor.authorLin, CW-
dc.contributor.authorNycholat, CM-
dc.contributor.authorMcBride, R-
dc.contributor.authorLiang, W-
dc.contributor.authorPaulson, JC-
dc.contributor.authorMok, CKP-
dc.contributor.authorWilson, IA-
dc.date.accessioned2019-07-20T10:35:18Z-
dc.date.available2019-07-20T10:35:18Z-
dc.date.issued2019-
dc.identifier.citationCell Host & Microbe, 2019, v. 25 n. 6, p. 836-844.e5-
dc.identifier.issn1931-3128-
dc.identifier.urihttp://hdl.handle.net/10722/272081-
dc.description.abstractEgg-based seasonal influenza vaccines are the major preventive countermeasure against influenza virus. However, their effectiveness can be compromised when antigenic changes arise from egg-adaptive mutations on influenza hemagglutinin (HA). The L194P mutation is commonly observed in egg-based H3N2 vaccine seed strains and significantly alters HA antigenicity. An approach to prevent L194P would therefore be beneficial. We show that emergence of L194P during egg passaging can be impeded by preexistence of a G186V mutation, revealing strong incompatibility between these mutations. X-ray structures illustrate that individual G186V and L194P mutations have opposing effects on the HA receptor-binding site (RBS), and when both G186V and L194P are present, the RBS is severely disrupted. Importantly, wild-type HA antigenicity is maintained with G186V, but not L194P. Our results demonstrate that these epistatic interactions can be used to prevent the emergence of mutations that adversely alter antigenicity during egg adaptation.-
dc.languageeng-
dc.publisherCell Press. The Journal's web site is located at http://www.cellhostandmicrobe.com-
dc.relation.ispartofCell Host & Microbe-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectAntigenicity-
dc.subjectEgg-adaptive mutation-
dc.subjectEpistasis-
dc.subjectHemagglutinin-
dc.subjectInfluenza virus-
dc.subjectReceptor binding-
dc.subjectVaccine-
dc.titlePreventing an Antigenically Disruptive Mutation in Egg-Based H3N2 Seasonal Influenza Vaccines by Mutational Incompatibility-
dc.typeArticle-
dc.identifier.emailLv, H: huibinlv@hku.hk-
dc.identifier.emailNg, WWS: nwsprp@hku.hk-
dc.identifier.emailMok, CKP: ch02mkp@hkucc.hku.hk-
dc.identifier.authorityMok, CKP=rp01805-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.chom.2019.04.013-
dc.identifier.pmid31151913-
dc.identifier.scopuseid_2-s2.0-85066796436-
dc.identifier.hkuros298436-
dc.identifier.volume25-
dc.identifier.issue6-
dc.identifier.spage836-
dc.identifier.epage844.e5-
dc.identifier.isiWOS:000471116700010-
dc.publisher.placeUnited States-

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