YEN HL, Zhou J, Choy KT, Sia SF, et al. The R292 K mutation that confers resistance to neuraminidase inhibitors leads to competitive fitness loss of A/Shanghai/1/2013 (H7N9) influenza virus in ferrets.. J Infect Dis. 2014 Jun 20. pii: jiu353
BACKGROUND:
?The neuraminidase (NA) inhibitors are the only licensed therapeutic option for human zoonotic H7N9 infections. An NA-R292 K 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-R292 K 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-R292 K viruses transmitted at comparable efficiency to direct or respiratory droplet contact ferrets. In ferrets inoculated with the plaque-purified A/Shanghai/1/2013 NA-R292 K 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 while the resistant K292 genotype was more frequently detected in the lungs.
CONCLUSIONS:
?The NA inhibitor-resistant H7N9 virus with the NA-R292 K mutation may transmit among ferrets but showed compromised fitness in vivo while in competition with the wild-type virus.
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