Genetic Diversity of H5 High Pathogenicity Avian Influenza Viruses Detected in Laos, 2019-2024: Multiple Clades, Subtypes, and Genotypes

Since 2004, H5 high pathogenicity avian influenza viruses (HPAIVs) from several clades have caused outbreaks in Laos, with clade 2.3.2.1e H5N1 viruses predominating since 2015. However, genomic data on H5 HPAIVs circulating in Laos after 2018 remain limited. In this study, we performed whole-genome sequencing of 37 H5Nx HPAIVs isolated in Laos during 2019–2024 and investigated their genetic characteristics using phylogenetic analyses alongside publicly available Lao HPAIV sequences collected during 2015–2024. Based on gene constellations, 12 genotypes were identified across three HA clades: seven clade 2.3.2.1e genotypes (E1–E7), three clade 2.3.4.4b genotypes (B1–B3), and two clade 2.3.4.4h genotypes (H1–H2). Clade 2.3.2.1e H5N1 viruses predominated overall, and novel genotypes emerged through reassortment with 2.3.4.4b H5N1 and Eurasian low-pathogenicity avian influenza (LPAI) viruses. In contrast, 2.3.4.4b H5Nx and 2.3.4.4h H5N6 viruses were detected sporadically. Genetically related 2.3.2.1e H5N1 genotypes co-circulated in Laos, Cambodia, and Vietnam. Clade 2.3.4.4b H5N1 viruses detected in 2023 clustered with viruses detected in East Asia and North America since 2021. Genotype H2, a 2.3.4.4h H5N6 virus, was genetically similar to H5N6 viruses epidemiologically linked to a human infection in Laos and detected in poultry and humans in China. In addition, genotype E7 was continuously detected from 2022 to 2024 and had the same gene constellation as viruses associated with human and mammalian infections in Cambodia and Vietnam. These findings demonstrate persistent circulation and reassortment of H5 HPAIVs in Laos, highlighting the need for genomic surveillance to monitor zoonotic risk and transboundary transmission in Southeast Asia.