title: In vitro selection of influenza B viruses with reduced sensitivity to neuraminidase inhibitors.
abstract: We and others have previously isolated influenza B viruses with reduced sensitivity to neuraminidase (NA) inhibitors (oseltamivir and zanamivir) from patients who were never exposed to these drugs. It was unclear whether the NA substitutions found in these influenza B isolates arose spontaneously or were caused by selective pressure. Here, we obtained influenza B viruses with reduced NA inhibitor sensitivity by in vitro selection with NA inhibitors. We found that these viruses possessed the same NA substitutions as those previously found in viruses isolated from untreated patients. These results suggest that these NA substitutions were selected in patients who were treated with an NA inhibitor and that the resistant variants were then transmitted to others.
authors.affiliation: Department of Infectious Diseases, Graduate School of Medicine, University of Tokyo, Hongo, Bunkyo-ku, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Hatakeyama
authors.forename: M
authors.initials: M
authors.lastname: Ozawa
authors.forename: Y
authors.initials: Y
authors.lastname: Kawaoka
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D009981:Influenza B virus / Q000187:drug effects* / Q000201:enzymology*; D008826:Microbial Sensitivity Tests; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D053139:Oseltamivir / Q000494:pharmacology; D012692:Serial Passage; D053243:Zanamivir / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D053139:Oseltamivir; D009439:Neuraminidase; D053243:Zanamivir