title: Oseltamivir-resistant influenza a viruses circulating in Japan.
abstract: Surveillance studies of the influenza viruses circulating in Europe and other countries in 2007 and 2008 have revealed rates of resistance to oseltamivir of up to 67% among H1N1 viruses. In the present study, we examined 202 clinical samples obtained from patients infected with H1N1 virus in Japan in 2007 and 2008 for oseltamivir resistance and found that three were oseltamivir resistant (1.5%). The 50% inhibitory concentrations (IC(50)s), as measured by a sialidase inhibition assay with these drug-resistant viruses, were >100-fold higher than those of the nonresistant viruses (median IC(50), 12.6 nmol/liter). The His274Tyr (strain N2 numbering) mutation of the neuraminidase protein, which is known to confer oseltamivir resistance, was detected in these three isolates. Phylogenetic analysis showed that one virus belonged to a lineage that is composed of drug-resistant viruses isolated in Europe and North America and that the other two viruses independently emerged in Japan. Continued surveillance studies are necessary to observe whether these viruses will persist.
authors.affiliation: Department of Microbiology and Immunology, Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tamura
authors.forename: Keiko
authors.initials: K
authors.lastname: Mitamura
authors.forename: Masahiko
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Motoko
authors.initials: M
authors.lastname: Fujino
authors.forename: Mari
authors.initials: M
authors.lastname: Nirasawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kimura
authors.forename: Maki
authors.initials: M
authors.lastname: Kiso
authors.forename: Hideaki
authors.initials: H
authors.lastname: Shimizu
authors.forename: Chiharu
authors.initials: C
authors.lastname: Kawakami
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hiroi
authors.forename: Kazuro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Mami
authors.initials: M
authors.lastname: Hata
authors.forename: Hiroko
authors.initials: H
authors.lastname: Minagawa
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kimura
authors.forename: Satoko
authors.initials: S
authors.lastname: Kaneda
authors.forename: Shigeo
authors.initials: S
authors.lastname: Sugita
authors.forename: Taisuke
authors.initials: T
authors.lastname: Horimoto
authors.forename: Norio
authors.initials: N
authors.lastname: Sugaya
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000998:Antiviral Agents / Q000494:pharmacology*; D016000:Cluster Analysis; D024882:Drug Resistance, Viral; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D007251:Influenza, Human / Q000821:virology*; D020128:Inhibitory Concentration 50; D007564:Japan; D020125:Mutation, Missense; D009439:Neuraminidase / Q000235:genetics; D053139:Oseltamivir / Q000494:pharmacology*; D010802:Phylogeny; D017385:Sequence Homology; D014764:Viral Proteins / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D014764:Viral Proteins; D053139:Oseltamivir; D009439:Neuraminidase