tetano
Editor, Senior Moderator
J Antimicrob Chemother. 2015 Mar 18. pii: dkv065. [Epub ahead of print]
[h=1]Influenza viruses with B/Yamagata- and B/Victoria-like neuraminidases are differentially affected by mutations that alter antiviral susceptibility.[/h] Farrukee R[SUP]1[/SUP], Leang SK[SUP]2[/SUP], Butler J[SUP]2[/SUP], Lee RT[SUP]3[/SUP], Maurer-Stroh S[SUP]4[/SUP], Tilmanis D[SUP]2[/SUP], Sullivan S[SUP]2[/SUP], Mosse J[SUP]5[/SUP], Barr IG[SUP]2[/SUP], Hurt AC[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]OBJECTIVES:[/h] 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).
[h=4]METHODS:[/h] 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).
[h=4]RESULTS:[/h] 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.
[h=4]CONCLUSIONS:[/h] 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.
? 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.
[h=4]KEYWORDS:[/h] influenza B lineage; neuraminidase inhibitors; oseltamivir; resistance
PMID: 25786478 [PubMed - as supplied by publisher]
[h=1]Influenza viruses with B/Yamagata- and B/Victoria-like neuraminidases are differentially affected by mutations that alter antiviral susceptibility.[/h] Farrukee R[SUP]1[/SUP], Leang SK[SUP]2[/SUP], Butler J[SUP]2[/SUP], Lee RT[SUP]3[/SUP], Maurer-Stroh S[SUP]4[/SUP], Tilmanis D[SUP]2[/SUP], Sullivan S[SUP]2[/SUP], Mosse J[SUP]5[/SUP], Barr IG[SUP]2[/SUP], Hurt AC[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]OBJECTIVES:[/h] 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).
[h=4]METHODS:[/h] 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).
[h=4]RESULTS:[/h] 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.
[h=4]CONCLUSIONS:[/h] 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.
? 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.
[h=4]KEYWORDS:[/h] influenza B lineage; neuraminidase inhibitors; oseltamivir; resistance
PMID: 25786478 [PubMed - as supplied by publisher]