title: Pseudovirus-based neuraminidase inhibition assays reveal potential H5N1 drug-resistant mutations.
abstract: The use of antiviral drugs such as influenza neuraminidase (NA) inhibitors is a critical strategy to prevent and control flu pandemic, but this strategy faces the challenge of emerging drug-resistant strains. For a highly pathogenic avian influenza (HPAI) H5N1 virus, biosafety restrictions have significantly limited the efforts to monitor its drug responses and mechanisms involved. In this study, a rapid and biosafe assay based on NA pseudovirus was developed to study the resistance of HPAI H5N1 virus to NA inhibitor drugs. The H5N1 NA pseudovirus was comprehensively tested using oseltamivir-sensitive strains and their resistant mutants. Results were consistent with those in previous studies, in which live H5N1 viruses were used. Several oseltamivir-resistant mutations reported in human H1N1 were also identified to cause decreased oseltamivir sensitivity in H5N1 NA by using the H5N1 NA pseudovirus. Thus, H5N1 NA pseudoviruses could be used to monitor HPAI H5N1 drug resistance rapidly and safely.
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceuticals, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.forename: Taijiao
authors.initials: T
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001717:Birds; D024882:Drug Resistance, Viral / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D057809:HEK293 Cells; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity; D005585:Influenza in Birds / Q000188:drug therapy / Q000235:genetics / Q000821:virology; D007251:Influenza, Human / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D016297:Mutagenesis, Site-Directed; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000235:genetics; D053139:Oseltamivir / Q000008:administration & dosage
chemical_list: D004791:Enzyme Inhibitors; D053139:Oseltamivir; D009439:Neuraminidase