Avian HEV triggered egg decline: Viral-host, immune-neuroendocrine mechanisms in layers.

Abstract

Avian hepatitis E virus (aHEV), a member of the Hepeviridae family, poses substantial threats to poultry health and productivity, particularly through its detrimental impact on egg production in laying hens. This review elucidates the multifaceted mechanisms underlying aHEV-induced egg production decline in laying hens, focusing on direct viral-host interactions, immune dysregulation, and neuroendocrine disruption. aHEV exhibits strong tropism for reproductive organs, with active replication in ovarian tissues causing follicular apoptosis, structural damage, and hormonal imbalance. Viral proteins (ORF1-ORF3) drive pathogenesis through immune evasion, oxidative stress induction, and disruption of calcium metabolism. Notably, ORF2-mediated host receptor binding and ORF3-mediated viral egress synergistically impair ovarian function, while genotype-specific variations (e.g., gt3/gt5) influence tissue specificity and pathogenicity. Systemic inflammation and hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axis dysregulation further exacerbate reproductive dysfunction by altering gonadotropin signaling and estrogen synthesis. Despite advances in diagnostics (e.g., ORF2-based antigen assays) and limited vaccine development (e.g., China's Hecolin®), cross-protection against diverse aHEV genotypes remains inadequate. Emerging strains with enhanced virulence (e.g., SDXT20) and recombination potential highlight the urgent need for genotype-spanning interventions. We propose that antioxidant therapies, receptor-blocking strategies, and multi-epitope vaccines targeting conserved ORF2/ORF3 regions could mitigate aHEV's economic impact. Furthermore, unresolved questions regarding viral latency, transovarial transmission, and zoonotic risks necessitate integrated approaches combining organoid models, single-cell omics, and One Health surveillance to address this evolving challenge.