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Permissive changes in the neuraminidase play a dominant role in improving the viral fitness of oseltamivir-resistant seasonal influenza A(H1N1) strain

tetano

Editor, Senior Moderator
Antiviral Res. 2014 Dec 12. pii: S0166-3542(14)00346-5. doi: 10.1016/j.antiviral.2014.12.006. [Epub ahead of print]
[h=1]Permissive changes in the neuraminidase play a dominant role in improving the viral fitness of oseltamivir-resistant seasonal influenza A(H1N1) strains.[/h] Abed Y[SUP]1[/SUP], Pizzorno A[SUP]1[/SUP], Bouhy X[SUP]1[/SUP], Boivin G[SUP]2[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] Permissive neuraminidase (NA) substitutions such as R222Q, V234M and D344N have facilitated the emergence and worldwide spread of oseltamivir-resistant influenza A/Brisbane/59/2007 (H1N1)-H275Y viruses. However, the potential contribution of genetic changes in other viral segments on viral fitness remains poorly investigated. A series of recombinant A(H1N1)pdm09 and A/WSN/33 7:1 reassortants containing the wild-type (WT) A/Brisbane/59/2007 NA gene or its single (H275Y) and double (H275Y/Q222R, H275Y/M234V and H275Y/N344D) variants were generated and their replicative properties were assessed in vitro. The Q222R reversion substitution significantly reduced viral titers when evaluated in both A(H1N1)pdm09 and A/WSN/33 backgrounds. The permissive role of the R222Q was further confirmed using A/WSN/33 7:1 reassortants containing the NA gene of the oseltamivir-susceptible or oseltamivir-resistant influenza A/Mississippi/03/2001 strains. Therefore, NA permissive substitutions play a dominant role for improving viral replication of oseltamivir-resistant A (H1N1)-H275Y viruses in vitro.
Copyright ? 2014. Published by Elsevier B.V.


[h=4]KEYWORDS:[/h] Fitness; H1N1; Influenza; Neuraminidase; Oseltamivir; Resistance

PMID: 25512229 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/25512229
 
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