State Key Laboratory of Marine Environmental Science, State-Province Joint Engineering Laboratory of Marine Bioproducts and Technology, College of Ocean and Earth Sciences, Xiamen University, Xiamen 361102, China.
Key Laboratory of Fishery Drug Development of Ministry of Agriculture, Key Laboratory of Aquatic Animal Immune Technology of Guangdong Province, Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou 510380, China.
Viruses. 2022 Aug 6;14(8):1733. doi: 10.3390/v14081733.
Sirtuin 1 (SIRT1), a member of the class III lysine deacetylases, exhibits powerful functional diversity in physiological processes and disease occurrences. However, the potential molecular mechanism underlying the role of SIRT1 during viral infection in crustaceans is poorly understood. Herein, SIRT1 was functionally characterized from the red claw crayfish , which possesses typically conserved deacetylase domains and strong evolutionary relationships across various species. Moreover, gene knockdown of SIRT1 in crayfish haematopoietic tissue (Hpt) cell culture inhibited white spot syndrome virus (WSSV) late envelope gene transcription. In contrast, enhancement of deacetylase activity using a pharmacological activator promoted the replication of WSSV. Mechanically, SIRT1 was co-localized with viral envelope protein VP28 in the nuclei of Hpt cells and directly bound to VP28 with protein pulldown and co-immunoprecipitation assays. Furthermore, SIRT1 also interacted with another two viral envelope proteins, VP24 and VP26. To the best of our knowledge, this is the first report that WSSV structural proteins are linked to lysine deacetylases, providing a better understanding of the role of SIRT1 during WSSV infection and novel insights into the basic mechanism underlying the function of lysine deacetylases in crustaceans.
Sirtuin 1（SIRT1）是 III 类赖氨酸去乙酰化酶的成员，在生理过程和疾病发生中表现出强大的功能多样性。然而，SIRT1 在甲壳动物病毒感染中作用的潜在分子机制尚不清楚。本研究从红螯螯虾中对 SIRT1 进行了功能表征，该虾具有典型的保守去乙酰化酶结构域和与各种物种的强进化关系。此外，在螯虾造血组织（Hpt）细胞培养物中敲低 SIRT1 基因抑制了白斑综合征病毒（WSSV）晚期包膜基因的转录。相比之下，使用药理学激活剂增强去乙酰化酶活性促进了 WSSV 的复制。从机制上讲，SIRT1 与 Hpt 细胞核中的病毒包膜蛋白 VP28 共定位，并通过蛋白下拉和共免疫沉淀实验直接与 VP28 结合。此外，SIRT1 还与另外两种病毒包膜蛋白 VP24 和 VP26 相互作用。据我们所知，这是首例报道 WSSV 结构蛋白与赖氨酸去乙酰化酶相关的研究，为更好地理解 SIRT1 在 WSSV 感染中的作用以及赖氨酸去乙酰化酶在甲壳动物中的基本功能机制提供了新的认识。
