Co-Infection with Infectious Bursal Disease Virus Strains of Differing Virulence Induces Distinct Pathological Changes and Innate Antiviral Profiles in Three-Yellow Chickens

Infectious bursal disease virus (IBDV) strains of differing virulence co-circulate in poultry, yet the consequences of their coinfection remain incompletely understood. We compared clinical disease, strain-specific viral RNA loads, and host antiviral gene expression following single, dual, or triple infection of non-vaccinated Three-yellow chickens with the attenuated vaccine (att) IBDV strain B87, the very virulent (vv) IBDV strain NN1172, and the novel variant (nv) IBDV strain QZ191002. Mortality occurred only in groups receiving NN1172; the triple-coinfection group had the highest estimated cumulative mortality (37.04%) and the lowest bursa-to-body weight index (approximately 0.36) at 7 dpi. B87 viral RNA loads were significantly lower at 5–7 dpi in B87-containing coinfection groups than in B87 infection alone, whereas NN1172 and QZ191002 viral RNA loads did not differ significantly between their respective single- and coinfection groups. Relative to B87 single infection, B87 + NN1172 coinfection increased the mRNA expression of TLR3, IFN-β, OAS, Mx, and PKR at specific late time points and decreased Caspase-3 mRNA expression at 6 dpi. However, the antiviral gene expression levels examined did not differ significantly between NN1172 single infection and B87 + NN1172 coinfection. Overall, disease severity, viral RNA loads, and host antiviral gene expression varied according to the infecting strain combination, with NN1172 being the principal contributor to acute clinical disease under the experimental conditions examined. The findings of this study underscore the importance of considering strain-dependent interactions during IBDV co-infection under experimental conditions and may inform future studies on the prevention and control of IBDV.