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Dynamic Variation and Reversion in the Signature Amino Acids of H7N9 Virus During Human Infection

tetano

Editor, Senior Moderator
J Infect Dis. 2018 Apr 24. doi: 10.1093/infdis/jiy217. [Epub ahead of print]
[h=1]Dynamic Variation and Reversion in the Signature Amino Acids of H7N9 Virus During Human Infection.[/h] Zou X[SUP]1[/SUP], Guo Q[SUP]2[/SUP], Zhang W[SUP]3[/SUP], Chen H[SUP]2[/SUP], Bai W[SUP]3[/SUP], Lu B[SUP]1[/SUP], Zhang W[SUP]1[/SUP], Fan Y[SUP]1[/SUP], Liu C[SUP]1[/SUP], Wang Y[SUP]1[/SUP], Zhou F[SUP]1[/SUP], Cao B[SUP]1[/SUP]; , CAP-China Network.
[h=3]Author information[/h]

[h=3]Abstract[/h] [h=4]Background:[/h] Signature amino acids of H7N9 influenza virus play critical roles in human adaption and pathogenesis, but their dynamic variation is unknown during disease development.
[h=4]Methods:[/h] We sequentially collected respiratory samples from H7N9 patients at different timepoints and applied next-generation sequencing (NGS) to the whole genome of the H7N9 virus to investigate the variation at signature sites.
[h=4]Results:[/h] A total of 11 patients were involved and from whom 29 samples were successfully sequenced, including samples from multiple timepoints in 9 patients. NA R292K, PB2 E627K, and D701N were the three most dynamic mutations. The oseltamivir resistance-related NA R292K mutation was present in 9 samples from 5 patients, including one sample obtained before antiviral therapy. In all patients with the NA 292K mutation, the oseltamivir-sensitive 292R genotype persisted and was not eliminated by antiviral treatment. The PB2 E627K substitution was present in 18 samples from 8 patients, among which 12 samples demonstrated a mixture of E/K and the 627K frequency exhibited dynamic variation. Dual D701N and E627K mutations emerged but failed to achieve predominance in any of the samples.
[h=4]Conclusions:[/h] Signature amino acids in PB2 and NA demonstrated high polymorphism and dynamic variation within individual patients during H7N9 virus infection.


PMID: 29688498 DOI: 10.1093/infdis/jiy217
 
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