Rab20, a novel Rab small GTPase from orange-spotted grouper positively regulates host immune response against iridoviruses infection
Rab20, a novel Rab small GTPase from orange-spotted grouper positively regulates host immune response against iridoviruses infection
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DOI：
10.1016/j.aquaculture.2021.737534
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发表时间：
2022-01
期刊：
影响因子：
4.5
通讯作者：
Liqun Wang;Xinyue Zhang;Junrong Li;Min Yang;Qing Wang;Shina Wei;Lingfeng Guan;Q. Qin;Shaowen Wang
中科院分区：
文献类型：
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作者：
Liqun Wang;Xinyue Zhang;Junrong Li;Min Yang;Qing Wang;Shina Wei;Lingfeng Guan;Q. Qin;Shaowen Wang
Rab20是rabgtpase家族的一员，与膜转运和免疫应答有关，在细菌控制中起重要作用。然而，Rab20在病毒感染过程中的作用知之甚少。石斑鱼（Epinephelusspp.）在中国和东南亚国家广泛养殖，具有很高的经济价值。然而，养殖的石斑鱼遭受了由新加坡石斑鱼虹膜病毒（SGIV）等病毒引起的疾病，造成了巨大的经济损失。本研究研究了橙斑石斑鱼（Epinephelus coioides）一种新的Rab20同源物（EcRab20）在SGIV感染和宿主免疫应答中的作用。从哺乳动物到鱼类，EcRab20与其他Rab20序列具有较高的同源性。在健康石斑鱼中，EcRab20主要表达于免疫器官，如肾、肝和脾。感染SGIV后，脾脏中EcRab20的表达显著上调。共聚焦成像显示，EcRab20在细胞质中呈点状和囊泡状分布，其被显性阴性EcRab20 （DN EcRab20）过表达破坏。此外，EcRab20明显与高尔基体和早期核内体共定位，部分与内质网和晚期核内体共定位，但不与线粒体或溶酶体共定位。最终，EcRab20过表达显著抑制SGIV感染，而DN EcRab20过表达促进SGIV感染。此外，通过单粒子成像分析，我们发现EcRab20或DN EcRab20对SGIV的进入没有影响。此外，EcRab20正调控IFN免疫和炎症反应。综上所述，这些结果表明，EcRab20通过调节宿主免疫来影响SGIV感染，为Rab20抗SGIV感染的抗病毒机制提供了新的思路，有助于设计新的抗病毒策略。
Rab20, a member of the Rab GTPase family, associates with membrane trafficking and immune response, which play important roles in bacteria control. However, little is known about the role of Rab20 during virus infection. Groupers (Epinephelusspp.) with high economic value are widely cultured in China and Southeast Asian countries. However, the cultured groupers have suffered from diseases caused by viruses such as Singapore grouper iridovirus (SGIV) resulting in huge economic losses. In this study, the roles of a novel Rab20 homolog (EcRab20), from orange-spotted grouper (Epinephelus coioides), on the infection of SGIV and host immune response were investigated. EcRab20 showed high sequence identity with other Rab20 from mammals to fishes. In healthy groupers, EcRab20 was predominantly expressed in immune organs, such as kidney, liver and spleen. After SGIV infection, the expression of EcRab20 in spleen was significantly up-regulated. Confocal imaging showed that EcRab20 distributed in the cytoplasm as punctate and vesicle-like structures, which was destructed by overexpression of the dominant negative EcRab20 (DN EcRab20). Moreover, EcRab20 notably colocalized with Golgi and early endosomes, partly colocalized with endoplasmic reticulum and late endosomes, but did not colocalize with mitochondria or lysosome. Ultimately, overexpression of EcRab20 significantly inhibited SGIV infection, whereas overexpression of DN EcRab20 promoted SGIV infection. Furthermore, using single particle imaging analysis, we found that EcRab20 or DN EcRab20 had no effect on the entry of SGIV. In addition, EcRab20 positively regulated the IFN immune and inflammatory responses. Taken together, these results demonstrated that EcRab20 affect SGIV infection by regulating the host immunity, providing a new idea of the anti-virus mechanisms of Rab20 against SGIV infection and contributing to design new antiviral strategies.