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Influenza A(H1N1)pdm09 resistance and cross-decreased susceptibility to oseltamivir and zanamivir antiviral drugs

2014-07-21Journal article Restricted access
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dc.contributor.authorCorreia, V.
dc.contributor.authorSantos, L.
dc.contributor.authorGíria, M.
dc.contributor.authorAlmeida-Santos, M.
dc.contributor.authorRebelo-de-Andrade, H.
dc.date.accessioned2015-02-19T15:28:52Z
dc.date.available2015-02-19T15:28:52Z
dc.date.issued2014-07-21
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.por
dc.description.sponsorshipThis work was supported by a research grant from the Portuguese Calouste Gulbenkian Foundation and by doctoral grants from the Portuguese Science and Technology Foundation (SFRH/BD/48532/2008, SFRH/BD/62676/2009, and SFRH/BD/65211/2009).por
dc.identifier.citationJ Med Virol. 2015 Jan;87(1):45-56. doi: 10.1002/jmv.23986. Epub 2014 Jul 21por
dc.identifier.doi10.1002/jmv.23986
dc.identifier.issn0146-6615
dc.identifier.urihttp://hdl.handle.net/10400.18/2928
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherWileypor
dc.relation.publisherversionhttp://onlinelibrary.wiley.com/doi/10.1002/jmv.23986/abstractpor
dc.subjectA(H1N1) 2009 Pandemic Variantpor
dc.subjectNeuraminidase Inhibitorspor
dc.subjectSusceptibility Testingpor
dc.subjectNA H275Ypor
dc.subjectNA I223Vpor
dc.subjectPortugalpor
dc.subjectResistência aos Antimicrobianospor
dc.titleInfluenza A(H1N1)pdm09 resistance and cross-decreased susceptibility to oseltamivir and zanamivir antiviral drugspor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage56por
oaire.citation.startPage45por
oaire.citation.titleJournal of Medical Virologypor
oaire.citation.volume87(1)por
rcaap.rightsembargoedAccesspor
rcaap.typearticlepor

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