Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China.
Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, College of Marine Sciences, South China Agricultural University, Guangzhou, 510642, China.
Fish Shellfish Immunol. 2019 Nov;94:38-49. doi: 10.1016/j.fsi.2019.08.068. Epub 2019 Aug 27.
Peroxisome proliferator-activated receptor δ (PPAR-δ), also called PPAR-β or PPAR-β/δ, is a member of the peroxisome proliferator-activated receptor (PPAR) family, which belongs to the nuclear steroid receptor superfamily. Activated PPARs participate in the regulation of lipid and glucose metabolism and also affect cellular proliferation, differentiation, and apoptosis, and the immune responses. To investigate the roles of PPAR-δ in Singapore grouper iridovirus (SGIV) infection, we cloned and characterized the gene encoding a PPAR-δ homologue from the orange-spotted grouper, Epinephelus coioides (EcPPAR-δ). EcPPAR-δ encodes a 514-amino-acid polypeptide, with 95.29% and 74.76% homologue to the Seriola dumerili and human proteins, respectively. EcPPAR-δ contains a typical DNA-binding domain and a ligand-binding domain. Its expression was induced by SGIV infection in vitro. A subcellular localization analysis showed that EcPPAR-δ localizes throughout the cytoplasm and nucleus, with a diffuse intracellular expression pattern. SGIV replication was reduced by EcPPAR-δ overexpression, which was evident in the reduced severity of the cytopathic effect, reduced viral gene transcription, and the reduced expression of the viral capsid protein. The replication of SGIV increased with the knockdown of EcPPAR-δ. The overexpression and silencing of EcPPAR-δ in grouper spleen cells showed that EcPPAR-δ plays a positive role in the regulation of the interferon signaling pathway, but has an anti-inflammatory effect on the inflammatory response. The anti-inflammatory effect of EcPPAR-δ may be related to its function in maintaining cell homeostasis. Because the interferon signaling pathway plays an important role in antiviral immune responses, we speculate that the activation of the interferon signaling pathway by EcPPAR-δ overexpression underlies its inhibitory effect on SGIV replication. Together, our data greatly extend our understanding of the roles of the EcPPAR-δ family members in the pathogenesis of fish viruses.
过氧化物酶体增殖物激活受体 δ（PPAR-δ），也称为 PPAR-β 或 PPAR-β/δ，是过氧化物酶体增殖物激活受体（PPAR）家族的成员，属于核甾体受体超家族。激活的 PPARs 参与脂质和葡萄糖代谢的调节，还影响细胞增殖、分化和凋亡以及免疫反应。为了研究 PPAR-δ 在新加坡石斑鱼虹彩病毒（SGIV）感染中的作用，我们从橙斑石斑鱼（Epinephelus coioides）中克隆并鉴定了一个 PPAR-δ 同源基因。EcPPAR-δ 编码一个 514 个氨基酸的多肽，与 Seriola dumerili 和人类蛋白的同源性分别为 95.29%和 74.76%。EcPPAR-δ 包含一个典型的 DNA 结合域和一个配体结合域。它的表达在体外被 SGIV 感染诱导。亚细胞定位分析表明，EcPPAR-δ 定位于细胞质和细胞核中，具有弥漫的细胞内表达模式。EcPPAR-δ 的过表达降低了 SGIV 的复制，表现在细胞病变效应减轻、病毒基因转录减少和病毒衣壳蛋白表达减少。EcPPAR-δ 的敲低增加了 SGIV 的复制。EcPPAR-δ 在石斑鱼脾脏细胞中的过表达和沉默表明，EcPPAR-δ 在调控干扰素信号通路中发挥积极作用，但对炎症反应具有抗炎作用。EcPPAR-δ 的抗炎作用可能与其维持细胞内稳态的功能有关。由于干扰素信号通路在抗病毒免疫反应中起着重要作用，我们推测 EcPPAR-δ 过表达激活干扰素信号通路是其抑制 SGIV 复制的基础。总之，我们的数据极大地扩展了我们对 EcPPAR-δ 家族成员在鱼类病毒发病机制中的作用的认识。
