Influenza virus neuraminidase (NA) protein plays an essential role in facilitating viral release from infected cells. NA inhibitors have been the only therapeutic option for patients infected with H7N9 avian influenza virus – to date, there have been 450 laboratory-confirmed cases of H7N9 infections in humans. Although most infected patients become severely ill, sustained transmission from person to person has yet to be reported. If the H7N9 virus acquires the ability to transmit easily between humans, this could pose a major public health threat.
Recently, markers of drug resistance have been identified in some H7N9 clinical isolates. The development of drug resistance is problematic because it could make the available treatment options less effective. Hui-Ling Yen and colleagues assessed whether the NA-inhibitor resistant human influenza A H7N9 Shanghai/1 isolate (NA-R292K mutation) could be transmitted among ferrets. They demonstrate that the mutant (K292) strain is transmissible in ferrets at comparable efficiency to the wild type (R292), but has reduced replication fitness in vivo. In most ferret respiratory tissues the wild type strain was able to outcompete the mutant, except in the lung lobes where a significant percentage of the mutant K292 genotype was still detected. Taken together, these results suggest that although transmitted efficiently, the H7N9 Shanghai/1 mutant strain replicates with reduced efficiency in ferrets, and may not pose a significant public health concern.
However, further research and ongoing surveillance of NA-inhibitor treated persons infected with H7N9 influenza virus will be critical to fully understand how this mutation contributes to altered replication fitness in humans.