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Article: The PB2 Polymerase Host Adaptation Substitutions Prime Avian Indonesia Sub Clade 2.1 H5N1 Viruses for Infecting Humans

TitleThe PB2 Polymerase Host Adaptation Substitutions Prime Avian Indonesia Sub Clade 2.1 H5N1 Viruses for Infecting Humans
Authors
KeywordsCross species transmission
H5N1
Host adaptation
Influenza virus
PB2
RNP
Issue Date2019
PublisherMolecular Diversity Preservation International (MDPI) AG. The Journal's web site is located at http://www.mdpi.com/journal/viruses
Citation
Viruses, 2019, v. 11 n. 3, article no. 292 How to Cite?
AbstractSignificantly higher numbers of human infections with H5N1 virus have occurred in Indonesia and Egypt, compared with other affected areas, and it is speculated that there are specific viral factors for human infection with avian H5N1 viruses in these locations. We previously showed PB2-K526R is present in 80% of Indonesian H5N1 human isolates, which lack the more common PB2-E627K substitution. Testing the hypothesis that this mutation may prime avian H5N1 virus for human infection, we showed that: (1) K526R is rarely found in avian influenza viruses but was identified in H5N1 viruses 2–3 years after the virus emerged in Indonesia, coincident with the emergence of H5N1 human infections in Indonesia; (2) K526R is required for efficient replication of Indonesia H5N1 virus in mammalian cells in vitro and in vivo and reverse substitution to 526K in human isolates abolishes this ability; (3) Indonesian H5N1 virus, which contains K526R-PB2, is stable and does not further acquire E627K following replication in infected mice; and (4) virus containing K526R-PB2 shows no fitness deficit in avian species. These findings illustrate an important mechanism in which a host adaptive mutation that predisposes avian H5N1 virus towards infecting humans has arisen with the virus becoming prevalent in avian species prior to human infections occurring. A similar mechanism is observed in the Qinghai-lineage H5N1 viruses that have caused many human cases in Egypt; here, E627K predisposes towards human infections. Surveillance should focus on the detection of adaptation markers in avian strains that prime for human infection.
Persistent Identifierhttp://hdl.handle.net/10722/272004
ISSN
2017 Impact Factor: 3.761
2015 SCImago Journal Rankings: 1.873
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWang, P-
dc.contributor.authorSong, W-
dc.contributor.authorMok, BWY-
dc.contributor.authorZheng, M-
dc.contributor.authorLau, SY-
dc.contributor.authorLiu, S-
dc.contributor.authorChen, P-
dc.contributor.authorHuang, X-
dc.contributor.authorLiu, H-
dc.contributor.authorCremin, CJ-
dc.contributor.authorChen, H-
dc.date.accessioned2019-07-20T10:33:49Z-
dc.date.available2019-07-20T10:33:49Z-
dc.date.issued2019-
dc.identifier.citationViruses, 2019, v. 11 n. 3, article no. 292-
dc.identifier.issn1999-4915-
dc.identifier.urihttp://hdl.handle.net/10722/272004-
dc.description.abstractSignificantly higher numbers of human infections with H5N1 virus have occurred in Indonesia and Egypt, compared with other affected areas, and it is speculated that there are specific viral factors for human infection with avian H5N1 viruses in these locations. We previously showed PB2-K526R is present in 80% of Indonesian H5N1 human isolates, which lack the more common PB2-E627K substitution. Testing the hypothesis that this mutation may prime avian H5N1 virus for human infection, we showed that: (1) K526R is rarely found in avian influenza viruses but was identified in H5N1 viruses 2–3 years after the virus emerged in Indonesia, coincident with the emergence of H5N1 human infections in Indonesia; (2) K526R is required for efficient replication of Indonesia H5N1 virus in mammalian cells in vitro and in vivo and reverse substitution to 526K in human isolates abolishes this ability; (3) Indonesian H5N1 virus, which contains K526R-PB2, is stable and does not further acquire E627K following replication in infected mice; and (4) virus containing K526R-PB2 shows no fitness deficit in avian species. These findings illustrate an important mechanism in which a host adaptive mutation that predisposes avian H5N1 virus towards infecting humans has arisen with the virus becoming prevalent in avian species prior to human infections occurring. A similar mechanism is observed in the Qinghai-lineage H5N1 viruses that have caused many human cases in Egypt; here, E627K predisposes towards human infections. Surveillance should focus on the detection of adaptation markers in avian strains that prime for human infection.-
dc.languageeng-
dc.publisherMolecular Diversity Preservation International (MDPI) AG. The Journal's web site is located at http://www.mdpi.com/journal/viruses-
dc.relation.ispartofViruses-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectCross species transmission-
dc.subjectH5N1-
dc.subjectHost adaptation-
dc.subjectInfluenza virus-
dc.subjectPB2-
dc.subjectRNP-
dc.titleThe PB2 Polymerase Host Adaptation Substitutions Prime Avian Indonesia Sub Clade 2.1 H5N1 Viruses for Infecting Humans-
dc.typeArticle-
dc.identifier.emailWang, P: puiwang@hkucc.hku.hk-
dc.identifier.emailSong, W: wjsong@hkucc.hku.hk-
dc.identifier.emailMok, BWY: bobomok@hku.hk-
dc.identifier.emailLau, SY: sylau926@hkucc.hku.hk-
dc.identifier.emailLiu, S: siwenliu@hku.hk-
dc.identifier.emailChen, H: hlchen@hku.hk-
dc.identifier.authorityChen, H=rp00383-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3390/v11030292-
dc.identifier.pmid30909490-
dc.identifier.pmcidPMC6480796-
dc.identifier.scopuseid_2-s2.0-85063712546-
dc.identifier.hkuros298555-
dc.identifier.volume11-
dc.identifier.issue3-
dc.identifier.spagearticle no. 292-
dc.identifier.epagearticle no. 292-
dc.identifier.isiWOS:000464401100001-
dc.publisher.placeSwitzerland-

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