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- Title
The R292K Mutation That Confers Resistance to Neuraminidase Inhibitors Leads to Competitive Fitness Loss of A/Shanghai/1/2013 (H7N9) Influenza Virus in Ferrets.
- Authors
Yen, Hui-Ling; Zhou, Jie; Choy, Ka-Tim; Sia, Sin Fun; Teng, Ooiean; Ng, Iris H.; Fang, Vicky J.; Hu, Yunwen; Wang, Wei; Cowling, Benjamin J.; Nicholls, John M.; Guan, Yi; Peiris, Joseph Sriyal Malik
- Abstract
Background Neuraminidase (NA) inhibitors are the only licensed therapeutic option for human zoonotic H7N9 infections. An NA-R292K mutation that confers broad-spectrum resistance to NA inhibitors has been documented in H7N9 patients after treatment. Methods We evaluated the transmission potential of a human influenza A H7N9 isolate with a NA-R292K mutation in the ferret model followed by genotyping assay to monitor its competitive fitness in vivo. Results Plaque-purified A/Shanghai/1/2013 wild-type and NA-R292K viruses transmitted at comparable efficiency to direct or respiratory droplet contact ferrets. In ferrets inoculated with the plaque-purified A/Shanghai/1/2013 NA-R292K virus with dominant K292 (94%), the resistant K292 genotype was outgrown by the wild-type R292 genotype during the course of infection. Transmission of the resistant K292 genotype was detected in 3/4 direct contact and 3/4 respiratory droplet contact ferrets at early time points but was gradually replaced by the wild-type genotype. In the respiratory tissues of inoculated or infected ferrets, the wild-type R292 genotype dominated in the nasal turbinate, whereas the resistant K292 genotype was more frequently detected in the lungs. Conclusions The NA inhibitor-resistant H7N9 virus with the NA-R292K mutation may transmit among ferrets but showed compromised fitness in vivo while in competition with the wild-type virus.
- Subjects
INFLUENZA treatment; INFLUENZA transmission; GENETIC mutation; ISOLATION of biotechnological microorganisms; NEURAMINIDASE; DRUG resistance; FERRETS as laboratory animals; THERAPEUTICS
- Publication
Journal of Infectious Diseases, 2014, Vol 210, Issue 12, p1900
- ISSN
0022-1899
- Publication type
Article
- DOI
10.1093/infdis/jiu353