title: Pandemic 2009 H1N1 influenza A virus carrying a Q136K mutation in the neuraminidase gene is resistant to zanamivir but exhibits reduced fitness in the guinea pig transmission model.
abstract: Resistance of influenza A viruses to neuraminidase inhibitors can arise through mutations in the neuraminidase (NA) gene. We show here that a Q136K mutation in the NA of the 2009 pandemic H1N1 virus confers a high degree of resistance to zanamivir. Resistance is accompanied by reduced numbers of NA molecules in viral particles and reduced intrinsic enzymatic activity of mutant NA. Interestingly, the Q136K mutation strongly impairs viral fitness in the guinea pig transmission model.
authors.affiliation: Department of Virology, University of Freiburg, Freiburg, Germany.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Kaminski
authors.forename: Annette
authors.initials: A
authors.lastname: Ohnemus
authors.forename: Peter
authors.initials: P
authors.lastname: Staeheli
authors.forename: Dennis
authors.initials: D
authors.lastname: Rubbenstroth
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D024882:Drug Resistance, Viral; D006168:Guinea Pigs; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D009439:Neuraminidase / Q000235:genetics* / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000635:transmission / Q000821:virology; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics* / Q000378:metabolism; D053243:Zanamivir / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D050505:Mutant Proteins; D012367:RNA, Viral; D014764:Viral Proteins; D037521:Virulence Factors; C487630:NA protein, influenza A virus; D009439:Neuraminidase; D053243:Zanamivir