Molecular Characterization of Pathogenic Avian Reovirus Circulating in Clinically Affected Chickens in Southeastern China (2022–2023) and Its Immunosuppressive Interference with Fowl Adenovirus Serotype 4 Vaccination

Avian reovirus (ARV) is a ubiquitous pathogen in commercial poultry, traditionally associated with viral arthritis, malabsorption syndrome, and growth retardation. In recent years, the rapid genetic diversification of ARV has raised increasing concerns regarding vaccine mismatch, immune dysregulation, and complex disease outcomes in vaccinated flocks. In this study, an integrated investigation combining large-scale field surveillance, molecular characterization, and controlled animal experiments was conducted to elucidate the epidemiological features of ARV and its impact on heterologous vaccine-induced protection. Epidemiological surveillance revealed widespread ARV circulation in commercial poultry flocks, with marked genetic divergence between contemporary field isolates and classical vaccine strains. Phylogenetic analysis based on the <i>σC</i> gene demonstrated that the majority of circulating strains clustered within emerging genotypes that were genetically distinct from vaccine-related lineages. Using a controlled infection-vaccination-challenge model, prior ARV infection was shown to significantly impair humoral immune responses induced by an inactivated <i>Aviadenovirus hydropericardii</i> (fowl adenovirus serotype 4, FAdV-4) vaccine, as evidenced by reduced FAdV-4-specific antibody levels. Importantly, ARV pre-infection compromised vaccine-mediated protection and was associated with enhanced FAdV-4 pathogenicity following challenge, resulting in increased mortality, aggravated clinical manifestations, and more pronounced pathological lesions. These findings indicate that prior ARV infection is associated with reduced FAdV-4 vaccine-induced humoral responses and partial loss of protective efficacy under controlled experimental conditions. Importantly, this study provides quantitative experimental evidence using a defined infection-vaccination-challenge interference model rather than proposing a previously unrecognized virus-virus interaction. These results underscore the necessity of enhanced ARV surveillance and optimized immunization strategies in modern poultry production systems.