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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
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TitleThe 2008-2009 H1N1 influenza virus exhibits reduced susceptibility to antibody inhibition: implications for the prevalence of oseltamivir resistant variant viruses
 
AuthorsWu, WL2
Lau, SY2
Chen, Y1
Wang, G3
Mok, BWY2
Wen, X2
Wang, P2
Song, W2
Lin, T1
Chan, KH2
Yuen, KY2
Chen, HL2 3
 
KeywordsH1N1
Influenza
Neuraminidase
Oseltamivir
Resistance
H275Y
 
Issue Date2012
 
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/antiviral
 
CitationAntiviral Research, 2012, v. 93 n. 1, p. 144-153 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.antiviral.2011.11.006
 
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.
 
ISSN0166-3542
2013 Impact Factor: 3.434
2013 SCImago Journal Rankings: 1.512
 
DOIhttp://dx.doi.org/10.1016/j.antiviral.2011.11.006
 
PubMed Central IDPMC3243069
 
ISI Accession Number IDWOS:000300802100018
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorWu, WL
 
dc.contributor.authorLau, SY
 
dc.contributor.authorChen, Y
 
dc.contributor.authorWang, G
 
dc.contributor.authorMok, BWY
 
dc.contributor.authorWen, X
 
dc.contributor.authorWang, P
 
dc.contributor.authorSong, W
 
dc.contributor.authorLin, T
 
dc.contributor.authorChan, KH
 
dc.contributor.authorYuen, KY
 
dc.contributor.authorChen, HL
 
dc.date.accessioned2012-08-08T08:52:03Z
 
dc.date.available2012-08-08T08:52:03Z
 
dc.date.issued2012
 
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.
 
dc.description.naturelink_to_OA_fulltext
 
dc.identifier.citationAntiviral Research, 2012, v. 93 n. 1, p. 144-153 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.antiviral.2011.11.006
 
dc.identifier.citeulike10090132
 
dc.identifier.doihttp://dx.doi.org/10.1016/j.antiviral.2011.11.006
 
dc.identifier.epage153
 
dc.identifier.hkuros208499
 
dc.identifier.isiWOS:000300802100018
 
dc.identifier.issn0166-3542
2013 Impact Factor: 3.434
2013 SCImago Journal Rankings: 1.512
 
dc.identifier.issue1
 
dc.identifier.pmcidPMC3243069
 
dc.identifier.pmid22138712
 
dc.identifier.scopuseid_2-s2.0-84355165239
 
dc.identifier.spage144
 
dc.identifier.urihttp://hdl.handle.net/10722/157664
 
dc.identifier.volume93
 
dc.languageeng
 
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/antiviral
 
dc.publisher.placeNetherlands
 
dc.relation.ispartofAntiviral Research
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshYoung Adult
 
dc.subject.meshViral proteins - genetics - immunology - metabolism
 
dc.subject.meshPhylogeny
 
dc.subject.meshOseltamivir - pharmacology
 
dc.subject.meshOrthomyxoviridae infections - immunology
 
dc.subject.meshNeuraminidase - genetics - immunology - metabolism
 
dc.subject.meshMutation
 
dc.subject.meshMiddle aged
 
dc.subject.meshMice, Inbred BALB/c
 
dc.subject.meshMice
 
dc.subject.meshInfluenza A virus, H1N1 subtype - drug effects - genetics - immunology
 
dc.subject.meshHumans
 
dc.subject.meshGenotype
 
dc.subject.meshFemale
 
dc.subject.meshDrug resistance, Viral - genetics
 
dc.subject.meshCell line
 
dc.subject.meshAntiviral agents - pharmacology
 
dc.subject.meshAntibodies, Monoclonal - immunology
 
dc.subject.meshAnimals
 
dc.subject.meshAmino acid substitution
 
dc.subject.meshAdult
 
dc.subjectH1N1
 
dc.subjectInfluenza
 
dc.subjectNeuraminidase
 
dc.subjectOseltamivir
 
dc.subjectResistance
 
dc.subjectH275Y
 
dc.titleThe 2008-2009 H1N1 influenza virus exhibits reduced susceptibility to antibody inhibition: implications for the prevalence of oseltamivir resistant variant viruses
 
dc.typeArticle
 
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Author Affiliations
  1. Xiamen University
  2. The University of Hong Kong
  3. Shantou University