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, PR 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, PR China; Guangdong Provincial Key Laboratory for Aquatic Economic Animals, Sun Yat-sen University, Guangzhou, 510642, PR China.
Fish Shellfish Immunol. 2019 Nov;94:113-121. doi: 10.1016/j.fsi.2019.09.004. Epub 2019 Sep 3.
Autophagy related gene 16 (Atg16), which encodes a core protein for autophagosome formation, participates in autophagy activity, the ubiquitin proteasome system and inflammatory response in mammals. In this study, we cloned and characterized an Atg16 homolog from orange-spotted grouper (Epinephelus coioides) (EcAtg16L1). EcAtg16L1 encodes a 656-amino acid polypeptide, which shares 94.22% and 72.65% homology with large yellow croakers (Larimichthys crocea) and humans (Homo sapiens), respectively. EcAtg16L1 contains a conserved Atg16 domain and a WD-repeat-containing domain. Subcellular localization showed that EcAtg16L1 was distributed in the cytoplasm of grouper cells with a dot-like pattern. EcAtg16L1 overexpression promoted Singapore grouper iridovirus (SGIV) and red-spotted grouper nervous necrosis virus (RGNNV) replication, as evidenced by the increase in viral gene transcription and viral coat protein. Furthermore, EcAtg16L1 overexpression negatively regulated interferon (IFN)-related molecules and proinflammatory cytokines, and decreased IFN, IFN-stimulated response element, and nuclear factor κB promoter activities. Taken together, aside from its function in autophagosome formation, EcAtg16L1 also plays role in promoting SGIV and RGNNV replication and the pro-viral effect might involve its down regulation to interferon and inflammatory responses.
自噬相关基因 16（Atg16）编码自噬体形成的核心蛋白，参与哺乳动物的自噬活性、泛素蛋白酶体系统和炎症反应。在本研究中，我们从橙点石斑鱼（Epinephelus coioides）（EcAtg16L1）中克隆并鉴定了一个 Atg16 同源物。EcAtg16L1 编码一个 656 个氨基酸的多肽，与大黄鱼（Larimichthys crocea）和人类（Homo sapiens）分别具有 94.22%和 72.65%的同源性。EcAtg16L1 包含一个保守的 Atg16 结构域和一个 WD-重复结构域。亚细胞定位显示 EcAtg16L1 分布在石斑鱼细胞质中，呈点状。EcAtg16L1 的过表达促进了新加坡石斑鱼虹彩病毒（SGIV）和红鳍东方鲀神经坏死病毒（RGNNV）的复制，这表现在病毒基因转录和病毒外壳蛋白的增加。此外，EcAtg16L1 的过表达负调控干扰素（IFN）相关分子和促炎细胞因子，并降低 IFN、IFN 刺激反应元件和核因子 κB 启动子的活性。综上所述，除了在自噬体形成中的作用外，EcAtg16L1 还在促进 SGIV 和 RGNNV 复制方面发挥作用，其促病毒作用可能与其对干扰素和炎症反应的下调有关。
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