Lee N, Tang JW, Chon I, Kakuya F, Terao R, Kawashi. Influenza PA Substitutions and Genetic Diversity of A(H1N1)pdm09, A(H3N2), and B/Victoria Viruses in Japan During the 2023–2024 Season. Viruses. 2026; 18(1):13
We characterized influenza A(H1N1)pdm09, A(H3N2), and B/Victoria viruses circulating in Japan during 2023–2024, 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–September 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 ≈4–5 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’s 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 2023–2024, A(H1N1)pdm09 and B/Victoria remained genetically aligned with their vaccine components, whereas A(H3N2) shifted to the J lineage, consistent with the 2024–2025 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–clinical data support vaccine strain realignment for H3N2 and continued monitoring of baloxavir resistance in outpatient care.
See Also:
Latest articles in those days:
- [preprint]The mammalian-adaptive PB2-E627K substitution preserves viral fitness of clade 2.3.4.4b H5N1 HPAIV in birds 6 hours ago
- Mallard super-shedders of avian influenza exhibit distinct cloacal microbial abundance profiles 11 hours ago
- A digitally immune-optimized influenza vaccine broadly neutralizes swine and human H1N1 influenza viruses and protects from heterologous challenge 11 hours ago
- Associations between vaccine misinformation and influenza vaccine uptake: a population-based interrupted time-series study in China 11 hours ago
- Infection and transmission dynamics of bovine and human influenza A H5N1 viruses in mouse and hamster models 12 hours ago
[Go Top] [Close Window]


