{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T05:26:06Z","timestamp":1766726766351,"version":"3.48.0"},"reference-count":49,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,21]],"date-time":"2025-12-21T00:00:00Z","timestamp":1766275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["24wm0125005h005"],"award-info":[{"award-number":["24wm0125005h005"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Health Labour Sciences Research Grant by the Ministry of Health, Labour and Welfare, and Sci-ences, Japan","award":["24HA2005"],"award-info":[{"award-number":["24HA2005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>We characterized influenza A(H1N1)pdm09, A(H3N2), and B\/Victoria viruses circulating in Japan during 2023\u20132024, focusing on lineage placement relative to WHO-recommended vaccine strains and on baloxavir resistance (PA\/I38T substitutions). We enrolled 210 outpatients with influenza-like illness across eight clinics in six prefectures (October 2023\u2013September 2024). Of these, 209 had an analyzable pre-treatment respiratory specimen for RT-PCR; hemagglutinin (HA) and neuraminidase (NA) genes were sequenced by next-generation sequencing (NGS). PA\/I38T substitutions that confer baloxavir resistance were assessed by cycling-probe RT-PCR, Sanger sequencing, and NGS. HA phylogenies were constructed with global datasets and WHO vaccine reference strains. Of 209 pre-treatment specimens, 181 were influenza-positive (A(H1N1)pdm09 44.2%, A(H3N2) 37.6%, B\/Victoria 18.2%); 51 follow-up specimens were collected \u22484\u20135 days after baloxavir or neuraminidase inhibitor therapy. HA phylogeny placed A(H1N1)pdm09 in clades 5a.2a\/5a.2a.1 with predominance of subclade D.2. A(H3N2) clustered exclusively in clade 2a.3a.1 (J lineage, mostly J.1), indicating a mismatch with the season\u2019s A\/Darwin\/9\/2021 vaccine component and supporting the subsequent J-lineage update. All B\/Victoria genomes fell within V1A.3a.2 on a C.5 backbone (C.5.1 and C.5.7). No PA\/I38T variant was detected in any pre-treatment specimen. Post-baloxavir, PA\/I38T emerged in one A(H3N2) case (confirmed by all three methods) and in one B\/Victoria case detected by NGS only (minority variant in a low-load sample). NA genes showed no substitutions associated with reduced susceptibility to laninamivir (e.g., E119A, G147E). During 2023\u20132024, A(H1N1)pdm09 and B\/Victoria remained genetically aligned with their vaccine components, whereas A(H3N2) shifted to the J lineage, consistent with the 2024\u20132025 vaccine update. Although pre-treatment PA\/I38T was absent, low-frequency on-therapy selection was observed, including a rare PA\/I38T in influenza B\/Victoria detected by NGS, suggesting the value of deep sequencing when viral loads are low. These integrated genomic\u2013clinical data support vaccine strain realignment for H3N2 and continued monitoring of baloxavir resistance in outpatient care.<\/jats:p>","DOI":"10.3390\/v18010013","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T07:01:33Z","timestamp":1766386893000},"page":"13","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Influenza PA Substitutions and Genetic Diversity of A(H1N1)pdm09, A(H3N2), and B\/Victoria Viruses in Japan During the 2023\u20132024 Season"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1400-0864","authenticated-orcid":false,"given":"Nanjun","family":"Lee","sequence":"first","affiliation":[{"name":"Division of International Health (Public Health), Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4963-1028","authenticated-orcid":false,"given":"Julian W.","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Respiratory Sciences, University of Leicester, Leicester LE1 7RH, UK"},{"name":"Department of Clinical Microbiology, University Hospitals of Leicester NHS Trust, Leicester LE1 5WW, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1829-0686","authenticated-orcid":false,"given":"Irina","family":"Chon","sequence":"additional","affiliation":[{"name":"Division of International Health (Public Health), Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fujio","family":"Kakuya","sequence":"additional","affiliation":[{"name":"Furano Kyokai Hospital, Furano 076-8765, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryuta","family":"Terao","sequence":"additional","affiliation":[{"name":"Furano Kyokai Hospital, Furano 076-8765, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Kawashima","sequence":"additional","affiliation":[{"name":"Kawashima Medical Clinic, Shibukawa 377-0008, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isamu","family":"Sato","sequence":"additional","affiliation":[{"name":"Yoiko Pediatric Clinic, Niigata 950-0983, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Kodo","sequence":"additional","affiliation":[{"name":"Kodo Pediatrics, Uji 611-0013, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eitaro","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Suzuki Pediatric Clinic, Ube 755-0151, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hironori","family":"Masaki","sequence":"additional","affiliation":[{"name":"Masaki Respiratory Medicine Clinic, Nagasaki 850-0841, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norichika","family":"Asoh","sequence":"additional","affiliation":[{"name":"Juzenkai Hospital, Nagasaki 852-0812, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutaka","family":"Shirahige","sequence":"additional","affiliation":[{"name":"Shirahige Clinic, Nagasaki 850-0003, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirotsune","family":"Hamabata","sequence":"additional","affiliation":[{"name":"Awase-Daichi Clinic, Okinawa City 904-2172, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8198-0992","authenticated-orcid":false,"given":"Tsutomu","family":"Tamura","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Center of Niigata University in Myanmar (IDRC), Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keita","family":"Wagatsuma","sequence":"additional","affiliation":[{"name":"Division of International Health (Public Health), Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan"},{"name":"Institute for Research Administration, Niigata University, Niigata 951-8510, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6047-6734","authenticated-orcid":false,"given":"Yuyang","family":"Sun","sequence":"additional","affiliation":[{"name":"Division of International Health (Public Health), Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaming","family":"Li","sequence":"additional","affiliation":[{"name":"Division of International Health (Public Health), Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tri Bayu","family":"Purnama","sequence":"additional","affiliation":[{"name":"Division of International Health (Public Health), Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8450-8947","authenticated-orcid":false,"given":"Yusuke","family":"Ichikawa","sequence":"additional","affiliation":[{"name":"Division of International Health (Public Health), Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisami","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Center of Niigata University in Myanmar (IDRC), Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1554-8226","authenticated-orcid":false,"given":"Reiko","family":"Saito","sequence":"additional","affiliation":[{"name":"Division of International Health (Public Health), Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,21]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025, November 13). 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