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Article: The 2008-2009 H1N1 influenza virus exhibits reduced susceptibility to antibody inhibition: implications for the prevalence of oseltamivir resistant variant viruses

TitleThe 2008-2009 H1N1 influenza virus exhibits reduced susceptibility to antibody inhibition: implications for the prevalence of oseltamivir resistant variant viruses
Authors
KeywordsH1N1
Influenza
Neuraminidase
Oseltamivir
Resistance
H275Y
Issue Date2012
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/antiviral
Citation
Antiviral Research, 2012, v. 93 n. 1, p. 144-153 How to Cite?
Abstract
A naturally-occurring H275Y oseltamivir resistant variant of influenza A (H1N1) virus emerged in 2007, subsequently becoming prevalent worldwide, via an undetermined mechanism. To understand the antigenic properties of the H275Y variant, oseltamivir resistant and susceptible strains of H1N1 viruses were analyzed by hemagglutination inhibition (HI) and microneutralization assays. HI analysis with H1-positive sera obtained from seasonal flu vaccine immunized and non-immunized individuals, and H1-specific monoclonal antibodies, revealed that resistant strains exhibited a reduced reactivity to these antisera and antibodies in the HI assay, as compared to susceptible strains. Neutralization assay testing demonstrated that oseltamivir resistant H1N1 strains are also less susceptible to antibody inhibition during infection. Mice inoculated with a resistant clinical isolate exhibit 4-fold lower virus-specific antibody titers than mice infected with a susceptible strain under the same conditions. Resistant and sensitive variants of 2009 pandemic H1N1 virus did not exhibit such differences. While HA1 and NA phylogenetic trees show that both oseltamivir resistant and susceptible strains belong to clade 2B, NA D354G and HA A189T substitutions were found exclusively, and universally, in oseltamivir resistant variants. Our results suggest that the reduced susceptibility to antibody inhibition and lesser in vivo immunogenicity of the oseltamivir resistant 2008-2009 H1N1 influenza A virus is conferred by coupled NA and HA mutations, and may contribute to the prevalence of this H1N1 variant. © 2011 Elsevier B.V.
Persistent Identifierhttp://hdl.handle.net/10722/157664
ISSN
2013 Impact Factor: 3.434
2013 SCImago Journal Rankings: 1.512
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWu, WLen_US
dc.contributor.authorLau, SYen_US
dc.contributor.authorChen, Yen_US
dc.contributor.authorWang, Gen_US
dc.contributor.authorMok, BWYen_US
dc.contributor.authorWen, Xen_US
dc.contributor.authorWang, Pen_US
dc.contributor.authorSong, Wen_US
dc.contributor.authorLin, Ten_US
dc.contributor.authorChan, KHen_US
dc.contributor.authorYuen, KYen_US
dc.contributor.authorChen, HLen_US
dc.date.accessioned2012-08-08T08:52:03Z-
dc.date.available2012-08-08T08:52:03Z-
dc.date.issued2012en_US
dc.identifier.citationAntiviral Research, 2012, v. 93 n. 1, p. 144-153en_US
dc.identifier.issn0166-3542en_US
dc.identifier.urihttp://hdl.handle.net/10722/157664-
dc.description.abstractA naturally-occurring H275Y oseltamivir resistant variant of influenza A (H1N1) virus emerged in 2007, subsequently becoming prevalent worldwide, via an undetermined mechanism. To understand the antigenic properties of the H275Y variant, oseltamivir resistant and susceptible strains of H1N1 viruses were analyzed by hemagglutination inhibition (HI) and microneutralization assays. HI analysis with H1-positive sera obtained from seasonal flu vaccine immunized and non-immunized individuals, and H1-specific monoclonal antibodies, revealed that resistant strains exhibited a reduced reactivity to these antisera and antibodies in the HI assay, as compared to susceptible strains. Neutralization assay testing demonstrated that oseltamivir resistant H1N1 strains are also less susceptible to antibody inhibition during infection. Mice inoculated with a resistant clinical isolate exhibit 4-fold lower virus-specific antibody titers than mice infected with a susceptible strain under the same conditions. Resistant and sensitive variants of 2009 pandemic H1N1 virus did not exhibit such differences. While HA1 and NA phylogenetic trees show that both oseltamivir resistant and susceptible strains belong to clade 2B, NA D354G and HA A189T substitutions were found exclusively, and universally, in oseltamivir resistant variants. Our results suggest that the reduced susceptibility to antibody inhibition and lesser in vivo immunogenicity of the oseltamivir resistant 2008-2009 H1N1 influenza A virus is conferred by coupled NA and HA mutations, and may contribute to the prevalence of this H1N1 variant. © 2011 Elsevier B.V.en_US
dc.languageengen_US
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/antiviralen_US
dc.relation.ispartofAntiviral Researchen_US
dc.subjectH1N1-
dc.subjectInfluenza-
dc.subjectNeuraminidase-
dc.subjectOseltamivir-
dc.subjectResistance-
dc.subjectH275Y-
dc.subject.meshYoung Adulten_US
dc.subject.meshViral proteins - genetics - immunology - metabolismen_US
dc.subject.meshPhylogenyen_US
dc.subject.meshOseltamivir - pharmacologyen_US
dc.subject.meshOrthomyxoviridae infections - immunologyen_US
dc.subject.meshNeuraminidase - genetics - immunology - metabolismen_US
dc.subject.meshMutationen_US
dc.subject.meshMiddle ageden_US
dc.subject.meshMice, Inbred BALB/cen_US
dc.subject.meshMiceen_US
dc.subject.meshInfluenza A virus, H1N1 subtype - drug effects - genetics - immunologyen_US
dc.subject.meshHumansen_US
dc.subject.meshGenotypeen_US
dc.subject.meshFemaleen_US
dc.subject.meshDrug resistance, Viral - geneticsen_US
dc.subject.meshCell lineen_US
dc.subject.meshAntiviral agents - pharmacologyen_US
dc.subject.meshAntibodies, Monoclonal - immunologyen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAmino acid substitutionen_US
dc.subject.meshAdulten_US
dc.titleThe 2008-2009 H1N1 influenza virus exhibits reduced susceptibility to antibody inhibition: implications for the prevalence of oseltamivir resistant variant virusesen_US
dc.typeArticleen_US
dc.identifier.emailWu, WL: hazelwu@hkucc.hku.hken_US
dc.identifier.emailLau, SY: sylau926@hkucc.hku.hken_US
dc.identifier.emailMok, BWY: bobomok@hkucc.hku.hk-
dc.identifier.emailWang, P: puiwang@hkucc.hku.hk-
dc.identifier.emailSong, W: wjsong@hkucc.hku.hk-
dc.identifier.emailChan, KH: chankh2@hkucc.hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hku.hk-
dc.identifier.emailChen, HL: hlchen@hku.hk-
dc.identifier.authorityYuen, KY=rp00366en_US
dc.identifier.authorityChen, HL=rp00383en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1016/j.antiviral.2011.11.006en_US
dc.identifier.pmid22138712en_US
dc.identifier.pmcidPMC3243069-
dc.identifier.scopuseid_2-s2.0-84355165239en_US
dc.identifier.hkuros208499-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84355165239&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume93en_US
dc.identifier.issue1en_US
dc.identifier.spage144en_US
dc.identifier.epage153en_US
dc.identifier.isiWOS:000300802100018-
dc.publisher.placeNetherlandsen_US
dc.identifier.scopusauthoridChen, H=26643315400en_US
dc.identifier.scopusauthoridYuen, KY=36078079100en_US
dc.identifier.scopusauthoridChan, KH=7406034307en_US
dc.identifier.scopusauthoridLin, T=7404860987en_US
dc.identifier.scopusauthoridSong, W=23490429800en_US
dc.identifier.scopusauthoridWang, P=13907209900en_US
dc.identifier.scopusauthoridWen, X=36060825600en_US
dc.identifier.scopusauthoridMok, BWY=36786012800en_US
dc.identifier.scopusauthoridWang, G=54792324800en_US
dc.identifier.scopusauthoridChen, Y=35573045900en_US
dc.identifier.scopusauthoridLau, SY=35083705100en_US
dc.identifier.scopusauthoridWu, WL=36674119200en_US
dc.identifier.citeulike10090132-

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