- Title
- Influenza viruses with B/Yamagata- and B/Victoria-like neuraminidases are differentially affected by mutations that alter antiviral susceptibility
- Creator
- Farrukee, Rubaiyea; Leang, Sookkwan; Butler, Jeff; Lee, Raphael; Maurer-Stroh, Sebastian; Tilmanis, Danielle; Sullivan, Sheena; Mosse, Jennifer; Barr, Ian; Hurt, Aeron
- Date
- 2015
- Type
- Text; Journal article
- Identifier
- http://researchonline.federation.edu.au/vital/access/HandleResolver/1959.17/163945
- Identifier
- vital:12923
- Identifier
-
https://doi.org/10.1093/jac/dkv065
- Identifier
- ISBN:0305-7453
- Abstract
- Objectives: 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.
- Relation
- Journal of Antimicrobial Chemotherapy Vol. 70, no. 7 (2015), p. 2004-2012
- Rights
- © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
- Rights
- This metadata is freely available under a CCO license
- Subject
- 1115 Pharmacology and Pharmaceutical Sciences; 0605 Microbiology; 1108 Medical Microbiology; Influenza B lineage; Neuraminidase inhibitors; Oseltamivir; Resistance
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