Zhan Zhouling, Chen Hong, Liao Xinyu, Wu Siting, Lei Xiaoxia, Xu Qiongyue, Cao Helong, Qin Qiwei, Wei Jingguang
College of Marine Sciences, South China Agricultural University, Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, China.
College of Marine Sciences, South China Agricultural University, Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, 510642, China; Nansha-South China Agricultural University Fishery Research Institute, Guangzhou, Guangzhou, 511400, China; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, 266000, China.
Fish Shellfish Immunol. 2024 Sep;152:109774. doi: 10.1016/j.fsi.2024.109774. Epub 2024 Jul 16.
Singapore grouper iridovirus (SGIV) belongs to the family Iridoviridae and the genus Ranavirus, which is a large cytoplasmic DNA virus. Infection of grouper with SGIV can cause hemorrhage and swelling of the spleen of the fish. Previous work on genome annotation demonstrated that SGIV contained numerous uncharacterized or hypothetical open reading frames (ORFs), whose functions remained largely unknown. In the present study, the protein encoded by SGIV ORF128 (VP128) was identified. VP128 is predominantly localized within the endoplasmic reticulum (ER). Overexpression of VP128 significantly promoted SGIV replication. VP128 inhibited the interferon (IFN)-3 promoter activity and mRNA level of IFN-related genes induced by poly(I:C), Epinephelus coioides cyclic GMP/AMP synthase (EccGAS)/stimulator of IFN genes (EcSTING), and TANK-binding kinase 1 (EcTBK1). Moreover, VP128 interacted with EcSTING and EcTBK1. The interaction between VP128 and EcSTING was independent of any specific structural domain of EcSTING. Together, our results demonstrated that SGIV VP128 negatively regulated the IFN response by inhibiting EcSTING-EcTBK1 signaling for viral evasion.
新加坡石斑鱼虹彩病毒（SGIV）属于虹彩病毒科蛙病毒属，是一种大型细胞质DNA病毒。石斑鱼感染SGIV会导致鱼脾脏出血和肿胀。先前关于基因组注释的研究表明，SGIV含有大量未表征或假设的开放阅读框（ORF），其功能在很大程度上仍然未知。在本研究中，鉴定了SGIV ORF128编码的蛋白（VP128）。VP128主要定位于内质网（ER）。VP128的过表达显著促进了SGIV的复制。VP128抑制了聚肌胞苷酸（poly(I:C)）、斜带石斑鱼环鸟苷酸/腺苷酸合成酶（EccGAS）/干扰素基因刺激因子（EcSTING）和TANK结合激酶1（EcTBK1）诱导的干扰素（IFN）-3启动子活性和IFN相关基因的mRNA水平。此外，VP128与EcSTING和EcTBK1相互作用。VP128与EcSTING之间的相互作用独立于EcSTING的任何特定结构域。总之，我们的结果表明，SGIV VP128通过抑制EcSTING-EcTBK1信号传导来负调控IFN反应，从而实现病毒逃逸。
