Neuraminidase mutations conferring resistance to oseltamivir in influenza A(H7N9) viruses

摘要: Human infections by avian influenza A(H7N9) virus entail substantial morbidity and mortality. Treatment of infected patients with the neuraminidase (NA) inhibitor oseltamivir was associated emergence viruses carrying NA substitutions. In inhibition (NI) assay, R292K conferred highly reduced oseltamivir, while E119V I222K each caused inhibition. To facilitate establishment laboratory correlates clinically relevant resistance, experiments were conducted in ferrets wild-type or variant genes recovered from A/Taiwan/1/2013 isolate. Oseltamivir treatment (5 25 mg/kg/dose) given 4 hours post-infection followed twice daily for 5 days. resulted a modest dose-dependent reduction (0.7–1.5 log 10 TCID 50 ) nasal wash viral titers inflammation response. Conversely, failed to significantly inhibit replication viruses. A small detected on day virus. Propensity resistance assessed oseltamivir-treated animals virus; 3 6 within 5–7 days post-infection. Collectively, we demonstrate that R292K, inhibitory activity not only NI but also ferrets, judged particularly loads washes, may signal need alternative therapeutics. Thus, these clinical outcomes measured ferret model correlate humans. Importance This report provides more evidence using assess susceptibility most prescribed anti-influenza drug. The information gained can be used assist human disease drug therapy. rapid treated well multiple reports this patients. Our findings highlight importance discovery characterization new antiviral drugs different mechanism action use combination strategies against emerging pandemic potential such as H7N9 virus, those markers.