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Influenza viruses with B/Yamagata- and B/Victoria-like neuraminidases are differentially affected by mutations that alter antiviral susceptibility

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dc.contributor.authorFarrukee, R.
dc.contributor.authorLeang, S.K.
dc.contributor.authorButler, J.
dc.contributor.authorLee, R.T.C.
dc.contributor.authorMaurer-Stroh, S.
dc.contributor.authorTilmanis, D.
dc.contributor.authorSullivan, S.
dc.contributor.authorMosse, J.
dc.contributor.authorBarr, I.G.
dc.contributor.authorHurt, A.C.
dc.date.issued2015
dc.description.abstractObjectives: The burden of disease due to influenza B is often underestimated. Clinical studies have shown that oseltamivir, a widely used neuraminidase inhibitor (NAI) antiviral drug, may have reduced effectiveness against influenza B viruses. Therefore, it is important to study the effect of neuraminidase mutations in influenza B viruses that may further reduce NAI susceptibility, and to determine whether these mutations have the same effect in the two lineages of influenza B viruses that are currently circulating (B/Yamagata-like and B/Victoria-like). Methods: We characterized the effect of 16 amino acid substitutions across five framework residues and four monomeric interface residues on the susceptibility to four different NAIs (oseltamivir, zanamivir, peramivir and laninamivir). Results: Framework residue mutations E117A and E117G conferred highly reduced inhibition to three of the four NAIs, but substantially reduced neuraminidase activity, whereas other framework mutations retained a greater level of NA activity. Mutations E105K, P139S and G140R of the monomeric interface were also found to cause highly reduced inhibition, but, interestingly, their effect was substantially greater in a B/Victoria-like neuraminidase than in a B/Yamagata-like neuraminidase, with some susceptibility values being up to 1000-fold different between lineages. Conclusions: The frequency and the effect of key neuraminidase mutations on neuraminidase activity and NAI susceptibility can differ substantially between the two influenza B lineages. Therefore, future surveillance, analysis and interpretation of influenza B virus NAI susceptibility should consider the B lineage of the neuraminidase in the same manner as already occurs for different influenza A neuraminidase subtypes.
dc.description.statementofresponsibilityRubaiyea Farrukee, Sook-Kwan Leang, Jeff Butler, Raphael T.C. Lee, Sebastian Maurer-Stroh, Danielle Tilmanis, Sheena Sullivan, Jennifer Mosse, Ian G. Barr and Aeron C. Hurt
dc.identifier.citationJournal of Antimicrobial Chemotherapy, 2015; 70(7):2004-2012
dc.identifier.doi10.1093/jac/dkv065
dc.identifier.issn0305-7453
dc.identifier.issn1460-2091
dc.identifier.orcidSullivan, S. [0000-0002-0856-0294]
dc.identifier.urihttp://hdl.handle.net/2440/120798
dc.language.isoen
dc.publisherOxford University Press
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1055793
dc.rights© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com
dc.source.urihttps://doi.org/10.1093/jac/dkv065
dc.subjectOseltamivir; neuraminidase inhibitors; resistance; influenza B lineage
dc.titleInfluenza viruses with B/Yamagata- and B/Victoria-like neuraminidases are differentially affected by mutations that alter antiviral susceptibility
dc.typeJournal article
pubs.publication-statusPublished

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