{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:30:03Z","timestamp":1792715403452,"version":"4.5.0"},"reference-count":25,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T00:00:00Z","timestamp":1430438400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Between September 2013 and July 2014, 2,482 influenza 2009 pandemic A(H1N1) [A(H1N1)pdm09] viruses were screened in Japan for the H275Y substitution in their neuraminidase (NA) protein, which confers cross-resistance to oseltamivir and peramivir. We found that a large cluster of the H275Y mutant virus was present prior to the main influenza season in Sapporo\n                    <jats:bold>\/<\/jats:bold>\n                    Hokkaido, with the detection rate for this mutant virus reaching 29% in this area. Phylogenetic analysis suggested the clonal expansion of a single mutant virus in Sapporo\n                    <jats:bold>\/<\/jats:bold>\n                    Hokkaido. To understand the reason for this large cluster, we examined the\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    properties of the mutant virus. We found that it grew well in cell culture, with growth comparable to that of the wild-type virus. The cluster virus also replicated well in the upper respiratory tract of ferrets and was transmitted efficiently between ferrets by way of respiratory droplets. Almost all recently circulating A(H1N1)pdm09 viruses, including the cluster virus, possessed two substitutions in NA, V241I and N369K, which are known to increase replication and transmission fitness. A structural analysis of NA predicted that a third substitution (N386K) in the NA of the cluster virus destabilized the mutant NA structure in the presence of the V241I and N369K substitutions. Our results suggest that the cluster virus retained viral fitness to spread among humans and, accordingly, caused the large cluster in Sapporo\/Hokkaido. However, the mutant NA structure was less stable than that of the wild-type virus. Therefore, once the wild-type virus began to circulate in the community, the mutant virus could not compete and faded out.\n                  <\/jats:p>","DOI":"10.1128\/aac.04836-14","type":"journal-article","created":{"date-parts":[[2015,2,17]],"date-time":"2015-02-17T22:01:46Z","timestamp":1424210506000},"page":"2607-2617","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":77,"title":["Characterization of a Large Cluster of Influenza A(H1N1)pdm09 Viruses Cross-Resistant to Oseltamivir and Peramivir during the 2013-2014 Influenza Season in Japan"],"prefix":"10.1128","volume":"59","author":[{"given":"Emi","family":"Takashita","sequence":"first","affiliation":[{"name":"Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maki","family":"Kiso","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiichiro","family":"Fujisaki","sequence":"additional","affiliation":[{"name":"Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaru","family":"Yokoyama","sequence":"additional","affiliation":[{"name":"Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Shirakura","sequence":"additional","affiliation":[{"name":"Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironori","family":"Sato","sequence":"additional","affiliation":[{"name":"Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takato","family":"Odagiri","sequence":"additional","affiliation":[{"name":"Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Kawaoka","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan"},{"name":"ERATO Infection-Induced Host Responses Project, Japan Science and Technology Agency, Saitama, Japan"},{"name":"Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan"},{"name":"Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin\u2014Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Tashiro","sequence":"additional","affiliation":[{"name":"Influenza Virus Research Center, National Institute of Infectious Diseases, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","unstructured":"World Health Organization. 2010. WHO guidelines for pharmacological management of pandemic influenza A(H1N1) 2009 and other influenza viruses. World Health Organization Geneva Switzerland. http:\/\/www.who.int\/csr\/resources\/publications\/swineflu\/h1n1_use_antivirals_20090820\/en\/."},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01339-05"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3851\/IMP1194"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1606.091623"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1703.101188"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/irv.12132"},{"key":"e_1_3_3_8_2","doi-asserted-by":"crossref","unstructured":"Lackenby A Hungnes O Dudman SG Meijer A Paget WJ Hay AJ Zambon MC. 2008. Emergence of resistance to oseltamivir among influenza A(H1N1) viruses in Europe. Euro Surveill 13:pii=8026. http:\/\/www.eurosurveillance.org\/ViewArticle.aspx?ArticleId=8026.","DOI":"10.2807\/ese.13.05.08026-en"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1187816"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.3851\/IMP1804"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002431"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.07242-12"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jis337"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004065"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02681-13"},{"key":"e_1_3_3_16_2","doi-asserted-by":"crossref","unstructured":"Takashita E Ejima M Itoh R Miura M Ohnishi A Nishimura H Odagiri T Tashiro M. 2014. A community cluster of influenza A(H1N1)pdm09 virus exhibiting cross-resistance to oseltamivir and peramivir in Japan November to December 2013. Euro Surveill 19:pii=20666. http:\/\/www.eurosurveillance.org\/ViewArticle.aspx?ArticleId=20666.","DOI":"10.2807\/1560-7917.ES2014.19.1.20666"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.22101"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/mst197"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2014.07.001"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08260"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.43.8.4139-4146.2005"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002914"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01549-13"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2101\/141006"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2015.02.003"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.06085-11"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.04836-14","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.04836-14","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T17:59:25Z","timestamp":1645466365000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.04836-14"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,5]]},"references-count":25,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2015,5]]}},"alternative-id":["10.1128\/AAC.04836-14"],"URL":"https:\/\/doi.org\/10.1128\/aac.04836-14","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,5]]},"assertion":[{"value":"2014-11-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-02-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-04-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}