Fitness Costs for Influenza B Viruses Carrying Neuraminidase Inhibitor-Resistant Substitutions: Underscoring the Importance of E119A and H274Y

摘要: Influenza B viruses cause annual outbreaks of respiratory illness in humans and are increasingly recognized as a major influenza-associated pediatric mortality. Neuraminidase (NA) inhibitors (NAIs) the only available therapy for patients infected with influenza viruses, potential emergence NAI-resistant is public health concern. The NA substitutions located within enzyme active site could not reduce NAI susceptibility virus but also affect fitness. In this study, we investigated effect single on fitness B/Yamanashi/166/1998 (Yamagata lineage). We generated recombinant containing either wild-type (WT) or substitution catalytic (R371K) framework (E119A, D198E, D198Y, I222T, H274Y, N294S) residues. assessed susceptibility, biochemical properties, protein expression, replication vitro differentiated normal human bronchial epithelial (NHBE) cells. Our results showed that four (D198E, conferred reduced inhibition by oseltamivir three R371K) highly oseltamivir, zanamivir, peramivir. All substitutions, except D198Y R371K, were genetically stable after seven passages MDCK Cell surface expression was significantly increased H274Y N294S substitutions. Viruses E119A, attenuated efficiency NHBE Overall, E119A possess comparable to NAI-susceptible virus, acquisition these should be closely monitored.