ArticleFrontiers in public health2026
H5N1 clade 2.3.2.1e lineage transition in Lao PDR during 2023-2024 associated with regional spread and human infection risk-associated receptor-binding features.
Article in Frontiers in public health, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
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's Democratic Republic (Lao PDR) live bird markets during 2023-2024. 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 K), 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.
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