Culture breakthrough enables goose circovirus (GoCV) isolation and pathogenic gosling modeling to uncover the association between viral infection and vaccine failure.

Goose circovirus (GoCV), recognized as the most economically significant immunosuppressive pathogen in global waterfowl production, causes considerable economic losses annually, and multiprovincial surveillance studies have documented high seroprevalence rates. The critical barrier to combating GoCV has persisted in the complete absence of viable in vitro culture systems, fundamentally limiting pathogenesis studies and vaccine development. In a breakthrough advancement, this study pioneers the first successful establishment of a stable primary goose embryo kidney (GEK) cell culture system for GoCV propagation, achieving sustained viral replication through innovative culture protocol optimization. Comprehensive virological characterization via synchronized growth curve analysis, transmission electron microscopy, and IFA quantification not only confirms efficient viral proliferation but also resolves longstanding debates regarding the intracellular replication mechanisms of GoCV, termed GoCV/369/2020. Pathogenesis trials involving gosling with the novel isolated GoCV revealed unprecedented clinicopathological correlations, revealing severe growth retardation, feather disorders, persistent fecal shedding, and biphasic organ damage progression from acute hypertrophy to chronic atrophy. Most critically, we provide the first experimental evidence linking GoCV infection to catastrophic vaccine failure, showing reductions in the antibody titers of avian influenza virus and Newcastle disease virus. This breakthrough has led to the establishment of poultry industry solutions, such as standardized viral isolation for diagnostics, optimized vaccination schedules, and targeted biosecurity against fecal-oral transmission. This study established a stable in vitro culture system and a pathogenic gosling model for GoCV, elucidating its replication, pathogenesis, and vaccine interference, providing crucial insights for future research and control strategies.