Wang Zhiyuan, Chen Yang, Chen Yanyan, Chen Rui, Wang Weiwei, Hu Shichen, Li Yihai, Chen Hongjun, Wei Ping, He Xiumiao
Guangxi Key Laboratory for Polysaccharide Materials and Modifications, School of Marine Sciences and Biotechnology, Guangxi Minzu University, Nanning, Guangxi, China.
Institute for Poultry Science and Health, Guangxi University, Nanning, Guangxi, China.
Front Cell Infect Microbiol. 2025 Jan 13;14:1529159. doi: 10.3389/fcimb.2024.1529159. eCollection 2024.
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.
干扰素调节因子7（IRF7）介导的I型干扰素抗病毒反应对于鸡在病毒感染后调节宿主至关重要。传染性法氏囊病病毒（IBDV）是一种双链RNA病毒，可在3至6周龄的鸡中诱导免疫抑制和高死亡率。先前的研究表明，IBDV感染会拮抗I型干扰素的产生，以促进病毒在细胞中的复制，而IRF7信号可能起重要作用。然而，IBDV阻断IRF7途径的潜在机制仍不清楚。在本研究中，我们发现，在感染超强毒IBDV（vvIBDV）而非弱毒IBDV期间，DF-1细胞中的IRF7和IFN-β表达受到抑制，而病毒继续复制。IRF7的过表达抑制IBDV复制，而敲低IRF7则促进IBDV复制。IRF7的过表达无法补偿vvIBDV感染细胞中的IRF7蛋白水平，这表明IRF7蛋白因IBDV感染而降解。通过使用抑制剂，发现IRF7的降解与蛋白酶体途径有关。进一步的研究表明，观察到IRF7与IBDV VP3蛋白相互作用并共定位。与IBDV感染结果一致，观察到IBDV VP3蛋白抑制IRF7-IFN-β表达，通过蛋白酶体途径影响IRF7蛋白的降解。所有这些结果表明，IBDV通过病毒VP3蛋白影响IRF7的表达和蛋白酶体降解来利用IRF7，以促进病毒在细胞中的复制。这些发现揭示了IBDV用于逃避宿主抗病毒防御的新机制。
