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J Antimicrob Chemother. 2015 Jul;70(7):2004-12. doi: 10.1093/jac/dkv065. Epub 2015 Mar 18.

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

Author information

1
WHO Collaborating Centre for Reference and Research on Influenza, Melbourne, VIC, Australia Monash University, School of Applied Sciences and Engineering, Churchill, VIC, Australia.
2
WHO Collaborating Centre for Reference and Research on Influenza, Melbourne, VIC, Australia.
3
Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), Singapore.
4
Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), Singapore National Public Health Laboratory, Communicable Diseases Division Ministry of Health, Singapore School of Biological Sciences, Nanyang Technological University, Singapore.
5
Monash University, School of Applied Sciences and Engineering, Churchill, VIC, Australia.
6
WHO Collaborating Centre for Reference and Research on Influenza, Melbourne, VIC, Australia Melbourne School of Population and Global Health, University of Melbourne, VIC, Australia aeron.hurt@influenzacentre.org.

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.

KEYWORDS:

influenza B lineage; neuraminidase inhibitors; oseltamivir; resistance

PMID:
25786478
DOI:
10.1093/jac/dkv065
[Indexed for MEDLINE]

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