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ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Molecular Viral Pathogenesis
Volume 14 - 2024 |
doi: 10.3389/fcimb.2024.1529159
This article is part of the Research Topic Cytokine Signaling and Innate Host Defense in Modulation of Viral Infections and The Viral Evasion View all articles
Infectious bursal disease virus affecting interferon regulatory factor 7 signaling through VP3 protein to facilitate viral replication
Provisionally accepted
Zhiyuan Wang
1
Yang Chen
1
Yanyan Chen
1*
Rui Chen
1*
Weiwei Wang
2
Shichen Hu
1*
Yihai Li
1*
HONGJUN CHEN
3
Ping Wei
2
Xiumiao He
1*- 1 Guangxi Minzu University, Guangxi, China
- 2 Guangxi University, Nanning, Guangxi Zhuang Region, China
- 3 Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, Shanghai Municipality, China
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.
Keywords: Infectious bursal disease virus (IBDV), Interferon Regulatory Factor 7 (IRF7), antiviral response, IBDV VP3 protein, viral replication
Received: 16 Nov 2024; Accepted: 23 Dec 2024.
Copyright: © 2024 Wang, Chen, Chen, Chen, Wang, Hu, Li, CHEN, Wei and He. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yanyan Chen, Guangxi Minzu University, Guangxi, China
Rui Chen, Guangxi Minzu University, Guangxi, China
Shichen Hu, Guangxi Minzu University, Guangxi, China
Yihai Li, Guangxi Minzu University, Guangxi, China
Xiumiao He, Guangxi Minzu University, Guangxi, China
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