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; Laboratory for Marine Biology and Biotechnology, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao, 266000, China; Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai, 528478, China.
Fish Shellfish Immunol. 2023 Sep;140:108990. doi: 10.1016/j.fsi.2023.108990. Epub 2023 Aug 7.
Singapore grouper iridovirus (SGIV) is a highly pathogenic Iridoviridae that causes hemorrhage and spleen enlargement in grouper. Despite previous genome annotation efforts, many open reading frames (ORFs) in SGIV remain uncharacterized, with largely unknown functions. In this study, we identified the protein encoded by SGIV ORF122, now referred to as VP122. Notably, overexpression of VP122 promoted SGIV replication. Moreover, VP122 exhibited antagonistic effects on the natural antiviral immune response through the cGAS-STING signaling pathway. It specifically inhibited the cGAS-STING-triggered transcription of various immune-related genes, including IFN1, IFN2, ISG15, ISG56, PKR, and TNF-α in GS cells. Additionally, VP122 significantly inhibited the activation of the ISRE promoter mediated by EccGAS and EcSTING but had no effect on EccGAS or EcSTING alone. Immunoprecipitation and Western blotting experiments revealed that VP122 specifically interacts with EcSTING but not EccGAS. Notably, this interaction between VP122 and EcSTING was independent of any specific domain of EcSTING. Furthermore, VP122 inhibited the self-interaction of EcSTING. Interestingly, VP122 did not affect the recruitment of EcTBK1 and EcIRF3 to the EcSTING complex. Collectively, our results demonstrate that SGIV VP122 targets EcSTING to evade the type I interferon immune response, revealing a crucial role for VP122 in modulating the host-virus interaction.
新加坡石斑鱼虹彩病毒（SGIV）是一种高致病性虹彩病毒科病毒，可引起石斑鱼出血和脾脏肿大。尽管之前进行了基因组注释工作，但 SGIV 中的许多开放阅读框（ORF）仍未被描述，其功能很大程度上未知。在本研究中，我们鉴定了 SGIV ORF122 编码的蛋白，现在称为 VP122。值得注意的是，VP122 的过表达促进了 SGIV 的复制。此外，VP122 通过 cGAS-STING 信号通路对天然抗病毒免疫反应表现出拮抗作用。它特异性地抑制 cGAS-STING 触发的各种免疫相关基因的转录，包括 GS 细胞中的 IFN1、IFN2、ISG15、ISG56、PKR 和 TNF-α。此外，VP122 显著抑制了由 EccGAS 和 EcSTING 介导的 ISRE 启动子的激活，但对单独的 EccGAS 或 EcSTING 没有影响。免疫沉淀和 Western blot 实验表明，VP122 特异性地与 EcSTING 相互作用，但不与 EccGAS 相互作用。值得注意的是，VP122 与 EcSTING 之间的这种相互作用不依赖于 EcSTING 的任何特定结构域。此外，VP122 抑制了 EcSTING 的自我相互作用。有趣的是，VP122 不影响 EcTBK1 和 EcIRF3 向 EcSTING 复合物的募集。总之，我们的结果表明，SGIV VP122 靶向 EcSTING 以逃避 I 型干扰素免疫反应，揭示了 VP122 在调节宿主-病毒相互作用中的关键作用。
