title: Y155H amino acid substitution in influenza A(H1N1)pdm09 viruses does not confer a phenotype of reduced susceptibility to neuraminidase inhibitors.
abstract: The Y155H amino acid substitution in the neuraminidase gene (NA) has previously been associated with highly reduced inhibition by neuraminidase inhibitors in the seasonal H1N1 influenza A virus which circulated in humans before the 2009 pandemic. During the 2012/13 epidemic season in Spain, two A(H1N1) pdm09 viruses bearing the specific Y155H substitution in the NA were detected and isolated from two patients diagnosed with severe respiratory syndrome and pneumonia requiring admission to the intensive care unit. Contrary to what was observed in the seasonal A(H1N1) viruses, neither of the Y155H A(H1N1) pdm09 viruses described here showed a phenotype of reduced inhibition by NAIs as determined by the neuraminidase enzyme inhibition assay (MUNANA). High-throughput sequencing of the NA of both Y155H viruses showed that they were composed to >99% of H155 variants. We believe that this report can contribute to a better understanding of the biological significance of amino acid substitutions in the neuraminidase protein with regard to susceptibility of influenza viruses to neuraminidase inhibitors. This is of critical importance for optimal management of influenza disease patients.
authors.affiliation: National Influenza Centre of Madrid, National Centre for Microbiology, Carlos III Health Institute, Majadahonda, Madrid, Spain.
authors.forename: U
authors.initials: U
authors.lastname: Perez-Sautu
authors.forename: F
authors.initials: F
authors.lastname: Pozo
authors.forename: I
authors.initials: I
authors.lastname: Cuesta
authors.forename: S
authors.initials: S
authors.lastname: Monzon
authors.forename: A
authors.initials: A
authors.lastname: Calderon
authors.forename: M
authors.initials: M
authors.lastname: Gonzalez
authors.forename: M
authors.initials: M
authors.lastname: Molinero
authors.forename: I
authors.initials: I
authors.lastname: Lopez-Miragaya
authors.forename: S
authors.initials: S
authors.lastname: Rey
authors.forename: A
authors.initials: A
authors.lastname: Cañizares
authors.forename: G
authors.initials: G
authors.lastname: Rodriguez
authors.forename: C
authors.initials: C
authors.lastname: Gonzalez-Velasco
authors.forename: A
authors.initials: A
authors.lastname: Lackenby
authors.forename: I
authors.initials: I
authors.lastname: Casas
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics*; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D053118:Influenza A Virus, H1N1 Subtype / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D007251:Influenza, Human / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D008297:Male; D008826:Microbial Sensitivity Tests; D009439:Neuraminidase / Q000235:genetics*; D053139:Oseltamivir / Q000494:pharmacology / Q000627:therapeutic use; D058873:Pandemics; D010641:Phenotype; D012367:RNA, Viral / Q000235:genetics; D012621:Seasons; D017422:Sequence Analysis, DNA; D013030:Spain / Q000453:epidemiology; D014764:Viral Proteins; D053243:Zanamivir / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D012367:RNA, Viral; D014764:Viral Proteins; D053139:Oseltamivir; C487630:NA protein, influenza A virus; D009439:Neuraminidase; D053243:Zanamivir