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The virus acquired several amino acid substitutions that were responsible for antigenic drift until the 2018\u20132019 influenza season. Viruses possessing mutations in the NA and PA proteins that cause reduced susceptibility to NA inhibitors and baloxavir marboxil, respectively, have been detected after antiviral treatment, albeit infrequently. Here, we analyzed HA, NA, and PA sequences derived from A(H1N1)pdm09 viruses that were isolated during the 2018\u20132019 and 2019\u20132020 influenza seasons in Japan. We found that A(H1N1)pdm09 viruses possessing the D187A and Q189E substitutions in HA emerged and dominated during the 2019\u20132020 season; these substitutions in the antigenic site Sb, a high potency neutralizing antibody-eliciting site for humans, changed the antigenicity of A(H1N1)pdm09 viruses. Furthermore, we found that isolates possessing the N156K substitution, which was predicted to affect the antigenicity of A(H1N1)pdm09 virus at the laboratory level, were detected at a frequency of 1.0% in the 2018\u20132019 season but 10.1% in the 2019\u20132020 season. These findings indicate that two kinds of antigenically drifted viruses\u2014N156K and D187A\/Q189E viruses\u2014co-circulated during the 2019\u20132020 influenza season in Japan.<\/jats:p>","DOI":"10.3390\/v15020535","type":"journal-article","created":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T03:09:21Z","timestamp":1676430561000},"page":"535","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Characterization of Influenza A(H1N1)pdm09 Viruses Isolated in the 2018\u20132019 and 2019\u20132020 Influenza Seasons in Japan"],"prefix":"10.3390","volume":"15","author":[{"given":"Takuma","family":"Soga","sequence":"first","affiliation":[{"name":"Division of Virology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, 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Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5414-8148","authenticated-orcid":false,"given":"Masafumi","family":"Seki","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Infection Control, Tohoku Medical and Pharmaceutical University, Sendai 983-8536, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natsuko","family":"Kasuya","sequence":"additional","affiliation":[{"name":"Nakagawa Ekimae Naika Clinic, Kanagawa 224-0001, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3122-9735","authenticated-orcid":false,"given":"Michiko","family":"Koga","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, 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53706, USA"},{"name":"Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan"},{"name":"Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo 162-8655, Japan"},{"name":"The University of Tokyo Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA), Minato-ku, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"D49","DOI":"10.1016\/j.vaccine.2008.07.039","article-title":"The Biology of Influenza Viruses","volume":"26","author":"Bouvier","year":"2008","journal-title":"Vaccine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"434","DOI":"10.4049\/jimmunol.115.2.434","article-title":"Host Defenses against Influenza Virus: The Role of 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