State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
Int J Mol Sci. 2017 Nov 14;18(11):2419. doi: 10.3390/ijms18112419.
Grass carp (Ctenopharyngodon idellus) is an important worldwide commercial freshwater culture species. However, grass carp reovirus (GCRV) causes serious hemorrhagic disease in fingerlings and yearlings of fishes. To understand the molecular pathogenesis of host cells during GCRV infection, intensive proteomic quantification analysis of lysine acetylation in Ctenopharyngodon idella kidney (CIK) cells was performed. Using dimethylation labeling-based quantitative proteomics, 832 acetylated proteins with 1391 lysine acetylation sites were identified in response to GCRV infection, among which 792 proteins with 1323 sites were quantifiable. Bioinformatics analysis showed that differentially expressed lysine acetylated proteins are involved in diverse cellular processes and associated with multifarious functions, suggesting that extensive intracellular activities were changed upon viral infection. In addition, extensive alterations on host-protein interactions at the lysine acetylation level were also detected. Further biological experiments showed that the histone deacetylases (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) could significantly suppress the GCRV replication. To our knowledge, this is the first to reveal the proteome-wide changes in host cell acetylome with aquatic virus infection. The results provided in this study laid a basis for further understanding the host response to aquareovirus infection in the post-translational modification aspect by regulating cell lysine acetylation conducive to viral replication.
草鱼(Ctenopharyngodon idellus)是一种重要的世界性淡水养殖品种。然而,草鱼呼肠孤病毒(GCRV)会导致鱼类鱼苗和幼鱼发生严重的出血性疾病。为了了解宿主细胞在 GCRV 感染过程中的分子发病机制,对草鱼肾脏(CIK)细胞中赖氨酸乙酰化的蛋白质组进行了深入的定量分析。通过基于二甲基化标记的定量蛋白质组学,鉴定到了 832 种在 GCRV 感染时发生乙酰化的蛋白,其中 792 种蛋白的 1323 个赖氨酸乙酰化位点可定量分析。生物信息学分析表明,差异表达的赖氨酸乙酰化蛋白参与多种细胞过程,并与多种功能相关,表明病毒感染后发生了广泛的细胞内活动改变。此外,还检测到宿主蛋白相互作用在赖氨酸乙酰化水平上的广泛改变。进一步的生物学实验表明,组蛋白去乙酰化酶(HDAC)抑制剂 suberoylanilide hydroxamic acid(SAHA)可以显著抑制 GCRV 的复制。据我们所知,这是首次揭示水生病毒感染后宿主细胞乙酰化组的全蛋白质组变化。本研究结果为进一步了解宿主对水产呼肠孤病毒感染的反应提供了基础,通过调节细胞赖氨酸乙酰化有利于病毒复制,从翻译后修饰方面进行研究。