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Influenza A(H1N1)pdm09 Resistance and Cross-Decreased Susceptibility to Oseltamivir and Zanamivir Antiviral Drugs

2015-01Journal article Open access
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dc.contributor.authorCorreia, V
dc.contributor.authorSantos, L
dc.contributor.authorGíria, M
dc.contributor.authorAlmeida-Santos, MM
dc.contributor.authorRebelo-de-Andrade, H
dc.date.accessioned2016-03-17T16:14:03Z
dc.date.available2016-03-17T16:14:03Z
dc.date.issued2015-01
dc.description.abstractNeuraminidase inhibitors (NAIs) oseltamivir and zanamivir are currently the only effective antiviral drugs available worldwide for the management of influenza. The potential development of resistance is continually threatening their use, rationalizing and highlighting the need for a close and sustained evaluation of virus susceptibility. This study aimed to analyze and characterize the phenotypic and genotypic NAIs susceptibility profiles of A(H1N1)pdm09 viruses circulating in Portugal from 2009 to 2010/2011. A total of 144 cases of A(H1N1)pdm09 virus infection from community and hospitalized patients were studied, including three suspected cases of clinical resistance to oseltamivir. Oseltamivir resistance was confirmed for two of the suspected cases. Neuraminidase (NA) H275Y resistant marker was found in viruses from both cases but for one it was only present in 26.2% of virus population, raising questions about the minimal percentage of resistant virus that should be considered relevant. Cross-decreased susceptibility to oseltamivir and zanamivir (2-4 IC50 fold-change) was detected on viruses from two potentially linked community patients from 2009. Both viruses harbored the NA I223V mutation. NA Y155H mutation was found in 18 statistical non-outlier viruses from 2009, having no impact on virus susceptibility. The mutations at NA N369K and V241I may have contributed to the significantly higher baseline IC50 value obtained to oseltamivir for 2010/2011 viruses, compared to viruses from the pandemic period. These results may contribute to a better understanding of the relationship between phenotype and genotype, which is currently challenging, and to the global assessment of A(H1N1)pdm09 virus susceptibility profile and baseline level to NAIs.pt_PT
dc.identifier.citationJ Med Virol. 2015 Jan;87(1):45-56pt_PT
dc.identifier.doi10.1002/jmv.23986pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.17/2426
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWileypt_PT
dc.subjectHCC PAT CLINpt_PT
dc.subjectAntiviral Agents/pharmacologypt_PT
dc.subjectDrug Resistance, Viralpt_PT
dc.subjectInfluenza A Virus, H1N1 Subtype/drug effectspt_PT
dc.subjectInfluenza A Virus, H1N1 Subtype/enzymologypt_PT
dc.subjectInfluenza A Virus, H1N1 Subtype/geneticspt_PT
dc.subjectInfluenza A Virus, H1N1 Subtype/isolation & purificationpt_PT
dc.subjectInfluenza, Human/virologypt_PT
dc.subjectInhibitory Concentration 50pt_PT
dc.subjectMutation, Missensept_PT
dc.subjectNeuraminidase/geneticspt_PT
dc.subjectOseltamivir/pharmacologypt_PT
dc.subjectPortugalpt_PT
dc.subjectViral Proteins/geneticspt_PT
dc.subjectZanamivir/pharmacologypt_PT
dc.titleInfluenza A(H1N1)pdm09 Resistance and Cross-Decreased Susceptibility to Oseltamivir and Zanamivir Antiviral Drugspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH/BD/48532/2008/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH/BD/62676/2009/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH/BD/65211/2009/PT
oaire.citation.endPage56pt_PT
oaire.citation.startPage45pt_PT
oaire.citation.titleJournal of Medical Virologypt_PT
oaire.fundingStreamSFRH
oaire.fundingStreamSFRH
oaire.fundingStreamSFRH
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublicationd4c6417a-5f75-4a9a-90d1-b66a307e48ac
relation.isProjectOfPublication7a7ea92d-0566-4f56-a28d-90f1345d5025
relation.isProjectOfPublication9313f4f0-8d7d-47d5-a1ff-998e1593ea56
relation.isProjectOfPublication.latestForDiscoveryd4c6417a-5f75-4a9a-90d1-b66a307e48ac

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