title: [Analysis of the Neuraminidase Amino Acid Sequences of Influenza A/H1N1pdm09, A/H3N2, and B Viruses Isolated from Influenza Patients in the 2013/14 Japanese Influenza Season].
abstract: BACKGROUND
  Neuraminidase (NA) is an essential surface protein for influenza virus replication. NA inhibitors are commonly used for the treatment of influenza patients in Japan. Several mutations that reduce the effect of NA inhibitors have been reported. We sequenced the whole NA segment of isolated virus from influenza patients and investigated the relation between the NA amino acid sequence and the 50% inhibitory concentration (IC50) of four NA inhibitors.
  
  
  METHODS
  A total of 20 viruses that showed high or low IC50 of NA inhibitors were selected from A/H1N1pdm09, A/H3N2, and B isolates from the viruses isolated from patients in the 2013-14 influenza season. Viral RNA was extracted and RT-PCR was done. The amplified genome was sequenced using a next generation sequencer", and the deduced amino acid sequences were analyzed.
  
  
  RESULTS
  Two A/H1N1pdm09 viruses that showed very high IC50 for oseltamivir (150 nM and 130 nM) contained the H275Y mutation. Otherwise, no significant relation was found between the NA amino acids and the IC50 of the four NA inhibitors. There was no significant relation between the NA amino acids and the IC50 of the four NA inhibitors for A/H3N2 viruses. The B viruses that showed a high IC50 for oseltamivir and laninamivir shared some amino acids. The B viruses that showed a high IC50 of zanamivir and peramivir also shared some amino acids. They were different from the shared amino acids found for oseltamivir and laninamivir.
  
  
  CONCLUSIONS
  The previously reported H275Y mutation that causes oseltamivir resistance was found in the two A/H1N1pdm09 viruses that showed a very high IC50 for oseltamivir. No additional NA amino acid sequences related to the IC50 of the four NA inhibitors was found. The meaning of the shared amino acids among B viruses that showed a high IC50 would be an interesting target for further investigation.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ikematsu
authors.forename: Yong
authors.initials: Y
authors.lastname: Chong
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Shirane
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Toh
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sasaki
authors.forename: Yui
authors.initials: Y
authors.lastname: Koga
authors.forename: Shinya
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Taeko
authors.initials: T
authors.lastname: Hotta
authors.forename: Takeshi
authors.initials: T
authors.lastname: Uchiumi
authors.forename: Donchon
authors.initials: D
authors.lastname: Kang
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D007251:Influenza, Human / Q000188:drug therapy / Q000821:virology*; D009154:Mutation; D009439:Neuraminidase / Q000235:genetics*; D020539:Sequence Analysis, Protein
chemical_list: D000998:Antiviral Agents; D009439:Neuraminidase