College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.
Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Maoming, 525000, China.
Cell Mol Biol Lett. 2024 May 31;29(1):83. doi: 10.1186/s11658-024-00598-2.
Senecavirus A (SVA) caused porcine idiopathic vesicular disease (PIVD) showing worldwide spread with economic losses in swine industry. Although some progress has been made on host factors regulating the replication of SVA, the role of Z-DNA binding protein 1 (ZBP1) remains unclear.
The expression of ZBP1 in SVA-infected 3D/421 cells was analyzed by quantitative real-time PCR (qRT-PCR) and western blot. Western blot and qRT-PCR were used to detect the effects of over and interference expression of ZBP1 on SVA VP2 gene and protein. Viral growth curves were prepared to measure the viral proliferation. The effect on type I interferons (IFNs), interferon-stimulated genes (ISGs), and pro-inflammatory cytokines in SVA infection was analyzed by qRT-PCR. Western blot was used to analysis the effect of ZBP1 on NF-κB signaling pathway and inhibitor are used to confirm.
ZBP1 is shown to inhibit the replication of SVA by enhancing NF-κB signaling pathway mediated antiviral response. SVA infection significantly up-regulated the expression of ZBP1 in 3D4/21 cells. Infection of cells with overexpression of ZBP1 showed that the replication of SVA was inhibited with the enhanced expression of IFNs (IFN-α, IFN-β), ISGs (ISG15, PKR, and IFIT1) and pro-inflammatory cytokines (IL-6, IL-8, and TNF-α), while, infected-cells with interference expression of ZBP1 showed opposite effects. Further results showed that antiviral effect of ZBP1 is achieved by activation the NF-κB signaling pathway and specific inhibitor of NF-κB also confirmed this.
ZBP1 is an important host antiviral factor in SVA infection and indicates that ZBP1 may be a novel target against SVA.
塞尼卡病毒 A（SVA）引起猪特发性水疱病（PIVD），在全球范围内传播，给养猪业造成了经济损失。虽然已经在宿主因素调节 SVA 复制方面取得了一些进展，但 Z-DNA 结合蛋白 1（ZBP1）的作用尚不清楚。
通过定量实时 PCR（qRT-PCR）和 Western blot 分析 SVA 感染的 3D/421 细胞中 ZBP1 的表达。Western blot 和 qRT-PCR 用于检测 ZBP1 过表达和干扰表达对 SVA VP2 基因和蛋白的影响。制备病毒生长曲线以测量病毒增殖。通过 qRT-PCR 分析 SVA 感染对 I 型干扰素（IFNs）、干扰素刺激基因（ISGs）和促炎细胞因子的影响。Western blot 用于分析 ZBP1 对 NF-κB 信号通路的影响，并用抑制剂进行验证。
结果表明，ZBP1 通过增强 NF-κB 信号通路介导的抗病毒反应来抑制 SVA 的复制。SVA 感染显著上调了 3D4/21 细胞中 ZBP1 的表达。过表达 ZBP1 的细胞感染显示 SVA 的复制受到抑制，同时 IFN-α、IFN-β、ISG15、PKR 和 IFIT1 等 IFNs 和 ISGs 的表达增强，而干扰 ZBP1 表达的感染细胞则表现出相反的效果。进一步的结果表明，ZBP1 的抗病毒作用是通过激活 NF-κB 信号通路实现的，NF-κB 的特异性抑制剂也证实了这一点。
ZBP1 是 SVA 感染中重要的宿主抗病毒因子，表明 ZBP1 可能是 SVA 的一个新靶点。
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