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猪 TAB1 对伪狂犬病病毒复制的抑制作用。

The inhibitory effect of swine TAB1 on the replication of pseudorabies virus.

机构信息

Shandong Key Laboratory of Animal Disease Control and Breeding/Key Laboratory of Livestock and Poultry Multi-omics of MARA, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan, China; College of Life Science, Shandong Normal University, Jinan, China.

Shandong Key Laboratory of Animal Disease Control and Breeding/Key Laboratory of Livestock and Poultry Multi-omics of MARA, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan, China.

出版信息

Vet Microbiol. 2024 Sep;296:110172. doi: 10.1016/j.vetmic.2024.110172. Epub 2024 Jul 2.

Abstract

TAK1-binding protein 1 (TAB1) assembles with TAK1 through its C-terminal domain, leading to the self-phosphorylation and activation of TAK1, which plays an important role in the activation of NF-κB and MAPK signaling pathway. Pseudorabies virus (PRV) is the pathogen of Pseudorabies (PR), which belongs to the Alphaherpesvirus subfamily and causes serious economic losses to the global pig industry. However, the impact of swine TAB1 (sTAB1) on PRV infection has not been reported. In this study, evidence from virus DNA copies, virus titer and western blotting confirmed that sTAB1 could inhibit PRV replication and knockout of sTAB1 by CRISPR-Cas9 gene editing system could promote PRV replication. Further mechanistic studies by real-time PCR and luciferase reporter gene assay demonstrated that sTAB1 could enhance the production of inflammatory factors and chemokines, IFN-β transcription level and IFN-β promoter activity after PRV infection. In summary, we clarify the underlying mechanism of sTAB1 in inhibiting PRV replication for the first time, which provides a new idea for preventing PRV infection and lays a foundation for PRV vaccine development.

摘要

TAK1 结合蛋白 1(TAB1)通过其 C 端结构域与 TAK1 组装,导致 TAK1 的自我磷酸化和激活,这在 NF-κB 和 MAPK 信号通路的激活中起着重要作用。伪狂犬病病毒(PRV)是伪狂犬病(PR)的病原体,属于 Alphaherpesvirinae 亚科,给全球养猪业造成了严重的经济损失。然而,猪 TAB1(sTAB1)对 PRV 感染的影响尚未报道。在这项研究中,通过病毒 DNA 拷贝、病毒滴度和 Western blot 验证了 sTAB1 可以抑制 PRV 复制,而 CRISPR-Cas9 基因编辑系统敲除 sTAB1 可以促进 PRV 复制。通过实时 PCR 和荧光素酶报告基因检测进一步的机制研究表明,sTAB1 可以增强炎症因子和趋化因子的产生、PRV 感染后 IFN-β 的转录水平和 IFN-β 启动子活性。总之,我们首次阐明了 sTAB1 抑制 PRV 复制的潜在机制,为预防 PRV 感染提供了新思路,为 PRV 疫苗的开发奠定了基础。

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