RESUMEN
Senecavirus A (SVA) induced porcine idiopathic vesicular disease (PIVD) has been spread worldwide due to persistent infection, causing economic losses in swine industry. Host factors play an important role in replication of SVA, while, the interaction of migration inhibitory factor (MIF) and the virus has not been verified. Here, MIF facilitates the replication of SVA by enhancing the glycolysis via hypoxia-inducible factor alpha (HIF-1α) was reported. SVA infection up-regulates the expression of MIF in 3D4/21 cells, and infection experiment of cells with overexpression and interference expression of MIF showed that MIF facilitates the replication of SVA. MIF promoted the glycolysis in SVA infection to facilitate its replication by enhancing the accumulation of lactate and decreasing the production of adenosine triphosphate (ATP) and inhibiting the expression of retinoic acid-inducible gene I (RIG-I), mitochondrial antiviral-signaling protein (MAVS), interferon regulatory factor 3 (IRF3), interferon-beta (IFN-ß), IFN-α, interferon-stimulating gene 15 (ISG15), and ISG56. Meanwhile, specific inhibitor verified MIF facilitates the replication of SVA by enhancing glycolysis. Further results showed MIF induces the increased expression of HIF-1α, which enhances MIF-induced glycolysis. These results provide new data on host factors in replication of SVA, as well as better understanding the role of MIF in virus infection.
RESUMEN
BACKGROUND: 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. METHODS: 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. RESULTS: 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-ß), 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. CONCLUSIONS: ZBP1 is an important host antiviral factor in SVA infection and indicates that ZBP1 may be a novel target against SVA.
