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Interferon regulatory factor 7 (IRF7)-mediated type I interferon antiviral response is crucial for regulating the host following viral infection in chickens. Infectious bursal disease virus (IBDV) is a double-stranded RNA virus that induces immune suppression and high mortality rates in chickens aged 3-6 weeks. Previous studies have shown that IBDV infection antagonizes the type I interferon production to facilitate viral replication in the cell, and IRF7 signaling might play an important role. However, the underlying mechanisms that enable IBDV to block the IRF7 pathway remain unclear. In this study, we found that IRF7 and IFN-β expression were suppressed in DF-1 cells during infection with very virulent IBDV (vvIBDV), but not with attenuated IBDV, while the virus continued to replicate. Overexpression of IRF7 inhibits IBDV replication while knocking down IRF7 promotes IBDV replication. Overexpression of IRF7 couldn't compensate the IRF7 protein level in vvIBDV-infected cells, which suggested that IRF7 protein was degraded by IBDV infection. By using inhibitors, the degradation of IRF7 was found to be related to the proteasome pathway. Further study revealed that IRF7 was observed to interact and colocalize with the IBDV VP3 protein. Consistent with IBDV infection results, IBDV VP3 protein was observed to inhibit the IRF7-IFN-β expression, affect the degradation of IRF7 protein via proteasome pathway. All these results suggest that the IBDV exploits IRF7 by affecting its expression and proteasome degradation via the viral VP3 protein to facilitate viral replication in the cells. These findings revealed a novel mechanism that IBDV uses to evade host antiviral defense. [ABSTRACT FROM AUTHOR]

Novel variant infectious bursal disease virus (nvIBDV) is an emerging pathotype that can cause sub‐clinical disease with severe, prolonged immunosuppression in young chickens. At present, two major pathotypes, including vvIBDV and nvIBDV, are prevailing in China. In this study, we propose that the nvIBDV is a new genotype (A2dB1b) and also first isolated and characterized a nvIBDV reassortant strain YL160304 (A2dB3) with segments A and B derived, respectively, from the nvIBDV and the HLJ‐0504‐like vvIBDV from yellow chickens in southern China. The YL160304 causes more extensive cytotropism and can infect specific‐pathogen‐free chicken embryos with severe subcutaneous hemorrhage. The pathogenicity of YL160304 to 4‐week‐old three‐yellow chickens was determined and compared with those of the nvIBDV QZ191002 and the HLJ‐0504‐like vvIBDV NN1172. Weight gain was significantly reduced in all the challenged birds. No clinical signs and associated mortality were observed in the birds challenged with QZ191002, while the mortalities in the birds challenged with NN1172 and YL160304 were 30% (3/10) and 10% (1/10), respectively. At 7 days postchallenge, the bursa was severely damaged and the percentage of peripheral blood B lymphocyte (PBBL) decreased significantly in all the challenged birds and the quantity of the viral RNA detected in the bursa was in accordance with the results of the histomorphometry and the depletion of PBBL. This study not only confirmed the emerging epidemic of the novel variant and its reassortant strains, but also discovered that the naturally reassortant nvIBDV strain with the segment B of HLJ 0504‐like vvIBDV can significantly enhance the pathogenicity to chickens. [ABSTRACT FROM AUTHOR]

Novel variant infectious bursal disease virus (nvIBDV) is an emerging genotype (A2dB1b) that can cause severe and prolonged immunosuppression in young chickens. Despite current commercial vaccines being proven to lack complete protection against nvIBDV, it remains unclear whether the oil emulsion inactivated vaccines (OEVs) of the homologous and heterologous virus or booster immunization can provide effective protection. In this study, OEVs with two types of nvIBDV isolates QZ191002 (A-nv/B-nv) and YL160304 (A-nv/B-HLJ0504-like) were prepared and evaluated the protective effects of OEVs plus the booster immunizations with different current commercial vaccines against the challenge of nvIBDVs. The results from vaccination-challenge experiments showed that nvIBDV could break through the protection provided by only one immunization dose of the commercial vaccines, with the protection rates ranging from 40% to 60%. Interestingly, even with booster immunization with different commercial vaccines, the protection rates could only be increased to 60%-80%. As expected, only the OEVs of the homologous virus could provide 100% protection against the homologous nvIBDV, which could induce high-level specific antibodies, ameliorate target organ damage, and significantly reduce the viral load of the bursal in the challenged chickens. Notably, YL160304-OEV performed better than QZ191002-OEV, providing 100% protection not only against the challenge of homologous strain but also against that of heterologous QZ191002 strain. Antibody levels of the immunized chickens gradually increased after a short decline and reached the highest level on the age of 28 days. Similarly, the percentages of lymphocytes CD4+, CD8+ T, and B in peripheral blood lymphocytes (PBLs) were significantly increased on 21 d and 28 d. Notably, despite the nvIBDV, OEVs initially induced a delayed responses in the early stages but ultimately reach higher levels of CD4+ and CD8+ T lymphocytes. The results of study suggest that even booster immunization with different commercial vaccines cannot provide complete protection against nvIBDV, while the OEVs made by the nvIBDVs can provide full protection. Moreover, YL160304-OEV exhibits a broader protective spectrum against different nvIBDV strains, making it a potential candidate for the development of new vaccine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Huang, Zhang, Qiao, Shi, Huang, Huang, Wei, Mo, He and Wei.)