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- Title
Dynamic Variation and Reversion in the Signature Amino Acids of H7N9 Virus During Human Infection.
- Authors
Zou, Xiaohui; Guo, Qiang; Zhang, Wei; Chen, Hui; Bai, Wei; Lu, Binghuai; Zhang, Wang; Fan, Yanyan; Liu, Chao; Wang, Yeming; Zhou, Fei; Cao, Bin; , CAP-China Network; community-acquired pneumonia-China Network
- Abstract
<bold>Background: </bold>Signature amino acids of H7N9 influenza A virus play critical roles in human adaption and pathogenesis, but their dynamic variation is unknown during disease development.<bold>Methods: </bold>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.<bold>Results: </bold>A total of 11 patients were involved, from whom 29 samples were successfully sequenced, including samples from multiple timepoints in 9 patients. Neuraminidase (NA) R292K, basic polymerase 2 (PB2) E627K, and D701N were the 3 most dynamic mutations. The oseltamivir resistance-related NA R292K mutation was present in 9 samples from 5 patients, including 1 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.<bold>Conclusions: </bold>Signature amino acids in PB2 and NA demonstrated high polymorphism and dynamic variation within individual patients during H7N9 virus infection.
- Subjects
AMINO acids; AMINO compounds; RESPIRATORY infections; INFLUENZA A virus, H7N9 subtype; VIRUS diseases
- Publication
Journal of Infectious Diseases, 2018, Vol 218, Issue 4, p586
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiy217