{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T07:16:17Z","timestamp":1788419777246,"version":"build-2803163510"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Public Health"],"abstract":"<jats:p>Highly pathogenic avian influenza (HPAI) H5N1 viruses clade 2.3.2.1e has re-emerged in the Indochinese Peninsula, raising concerns about regional spread and zoonotic risk. We characterized eight H5N1 viruses isolated from 32 environmental and poultry-derived samples collected in Lao People\u2019s Democratic Republic (Lao PDR) live bird markets during 2023\u20132024. Whole-genome and phylogenetic analyses showed that all isolates belonged to clade 2.3.2.1e and were distinct from the previously dominant Lao clade 2.3.2.1c, indicating lineage transition in poultry-associated viruses. The Lao isolates were distributed across regional sublineages rather than forming a single local cluster, suggesting repeated introductions and cross-border genetic connectivity. Segment-level nucleotide identities ranged from 97.2 to 99.9%, revealing a complex mosaic genotype constellation. All isolates retained the avian-associated glutamic acid residue at position 627 of polymerase basic protein 2 (PB2-627E) and the aspartic acid residue at position 701 of polymerase basic protein 2 (PB2-701D). Hemagglutinin (HA) analysis showed a conserved polybasic cleavage motif, PQRERRRKRGLF, and conserved HA1-123S, HA1-154N, HA1-263T, and HA2-497L, whereas isolate-level variation was observed at HA1-94, HA1-188, and HA1-223. Structural modeling and Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) analysis of a representative isolate further highlighted receptor binding site (RBS) associated HA features. Importantly, RBS-associated HA variation was detected despite the absence of lysine residue at position 627 of polymerase basic protein 2 (PB2-627\u202fK), suggesting that early molecular changes relevant to mammalian or human adaptation may arise before acquisition of canonical mammalian-adaptive polymerase mutations. These findings support sustained cross-border genomic surveillance and receptor-binding-focused characterization of H5N1 viruses circulating in Lao live bird markets.<\/jats:p>","DOI":"10.3389\/fpubh.2026.1923867","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:42:15Z","timestamp":1788417735000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["H5N1 clade 2.3.2.1e lineage transition in Lao PDR during 2023\u20132024 associated with regional spread and human infection risk-associated receptor-binding features"],"prefix":"10.3389","volume":"14","author":[{"given":"Duc Duong","family":"Than","sequence":"first","affiliation":[{"name":"Zoonosis Research Center, Department of Infection Biology, School of Medicine, Wonkwang University","place":["Iksan, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyoon","family":"Chang","sequence":"additional","affiliation":[{"name":"Zoonosis Research Center, Department of Infection Biology, School of Medicine, Wonkwang University","place":["Iksan, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute of Endemic Diseases, Seoul National University Medical Research Center","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Watthana","family":"Theppangna","sequence":"additional","affiliation":[{"name":"National Animal Health Laboratory","place":["Vientiane, Laos"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seon-Ju","family":"Yeo","sequence":"additional","affiliation":[{"name":"Institute of Endemic Diseases, Seoul National University Medical Research Center","place":["Seoul, Republic of Korea"]},{"name":"Department of Tropical Medicine and Parasitology, Department of Biomedical Sciences, College of Medicine, Seoul National University","place":["Seoul, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun","family":"Park","sequence":"additional","affiliation":[{"name":"Zoonosis Research Center, Department of Infection Biology, School of Medicine, Wonkwang University","place":["Iksan, Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.cell.2014.02.040","article-title":"Identification, characterization, and natural selection of mutations driving airborne transmission of a\/H5N1 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