title: Neuraminidase inhibitor susceptibility testing of influenza type B viruses in China during 2010 and 2011 identifies viruses with reduced susceptibility to oseltamivir and zanamivir.
abstract: Influenza type B viruses are responsible for substantial morbidity and mortality in humans. Antiviral drugs are an important supplement to vaccination for reducing the public health impact of influenza virus infections. Influenza B viruses are not sensitive to M2 inhibitors which limit the current therapeutic options to two neuraminidase inhibitors (NAIs), oseltamivir and zanamivir, which are licensed in many countries. Drug resistance is a public health concern which has necessitated monitoring of influenza virus drug susceptibilities through active global surveillance. Here, we report the results of drug susceptibility surveillance of influenza type B viruses (n=680) collected in mainland China during two calendar years, 2010 and 2011, assessed using functional neuraminidase (NA) inhibition (NI) assays. Four influenza B viruses exhibited reduced susceptibilities to oseltamivir, but not zanamivir, and shared the amino acid substitution I221T (ATC→ACC), at this conserved residue in the NA active site (I222T in N2 numbering). Additionally, a single virus with reduced susceptibility to both oseltamivir and zanamivir was identified and contained an amino acid substitution D197N (GAC→AAC) at another conserved residue in the NA active site (D198N in N2 numbering). This report underlies the importance of continued influenza antiviral susceptibility surveillance globally, even in countries where the use of NAIs has been low or non-existing.
authors.affiliation: Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention, Chinese Centre for Disease Control and Prevention, Beijing, China.
authors.forename: Dayan
authors.initials: D
authors.lastname: Wang
authors.forename: Katrina
authors.initials: K
authors.lastname: Sleeman
authors.forename: Weijuan
authors.initials: W
authors.lastname: Huang
authors.forename: Ha T
authors.initials: HT
authors.lastname: Nguyen
authors.forename: Marnie
authors.initials: M
authors.lastname: Levine
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Cheng
authors.forename: Xiyan
authors.initials: X
authors.lastname: Li
authors.forename: Minju
authors.initials: M
authors.lastname: Tan
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Xing
authors.forename: Xiyan
authors.initials: X
authors.lastname: Xu
authors.forename: Alexander I
authors.initials: AI
authors.lastname: Klimov
authors.forename: Larisa V
authors.initials: LV
authors.lastname: Gubareva
authors.forename: Yuelong
authors.initials: Y
authors.lastname: Shu
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002681:China / Q000453:epidemiology; D024882:Drug Resistance, Viral; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D009981:Influenza B virus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000302:isolation & purification; D007251:Influenza, Human / Q000453:epidemiology / Q000821:virology*; D008826:Microbial Sensitivity Tests; D020125:Mutation, Missense; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D053139:Oseltamivir / Q000494:pharmacology*; D053243:Zanamivir / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D053139:Oseltamivir; D009439:Neuraminidase; D053243:Zanamivir