白斑综合症病毒IE1诱导凡纳滨对虾STAT磷酸化的分子机制及功能研究

White spot syndrome virus (WSSV) is one of the major pathogens of shrimp aquaculture. So far, there is no effective method to control this virus. To successfully cure this disease, it is crucial to uncover the infection and pathogenesis of the virus and develop the potential targets of virus control. Interestingly, our recent studies showed that IE1 could induce the phosphorylatoion of Litopenaeus vannamei STAT by possibly recruiting cellular protein kinase. However, it remains unclear that which protein kinase phosphorylates STAT, how it mediates STAT phosphorylation and what kind of biological processes are regulated by this protein kinase-mediated STAT phosphorylation. Therefore, further attempts will be made to identify the protein kinase interacting with IE1 and to investigate its regulatory role in STAT phosphorylation and the regulated phosphorylation site, as well as to elucidate the roles of this protein kinase-mediated STAT phosphorylation in the regulation of viral gene transcription and cell proliferation and appotosis using proteomics and molecular biology techniques. We strongly believe that the outcome of this study will indicate the molecular mechanism and biological function of the IE1-induced STAT phosphorylation. It will also contribute to a depth understanding of the infection and pathogenesis of WSSV and provide new ideas and scientific proofs for its control.

白斑综合症病毒(WSSV)是危害对虾养殖的主要病原之一，至今对其仍无有效的防治方法。要成功解决这一病害问题，其中关键环节之一就是揭示WSSV感染和致病机理，寻找防治该病毒的潜在靶点。有趣的是，申请者最近研究发现，WSSV极早期蛋白IE1可能通过招募细胞内蛋白激酶诱导凡纳滨对虾STAT磷酸化。然而，究竟是哪种蛋白激酶采取何种作用方式磷酸化STAT，以及其介导的STAT磷酸化调控哪些生物学过程等科学问题尚不清楚。为此，本项目拟进一步采用蛋白质组学和分子生物学技术，鉴定与IE1相互作用的蛋白激酶，研究其对STAT磷酸化的调控作用和所调控的磷酸化位点，探索其介导的STAT磷酸化对病毒基因转录以及细胞增殖和凋亡的调控作用，以揭示IE1诱导STAT磷酸化的分子机制及生物学功能。预期成果将有助于人们深入认识WSSV感染和致病的分子机制，为病毒的防治提供新的思路和科学依据。

白斑综合症病毒(WSSV)是危害对虾养殖的主要病原之一，但人们目前对其与对虾宿主互作机制尚不清楚。项目组前期发现WSSV极早期蛋白IE1可诱导凡纳滨对虾STAT磷酸化激活。为此，本项目拟在此基础之上进一步采用蛋白质组学和分子生物学等技术路线系统深入地探究IE1诱导对虾STAT磷酸化的分子机制及功能。结果发现，IE1可能招募对虾LvSrc64B激酶诱导LvSTAT磷酸化。其中，IE1通过磷酸化酪氨酸基序Y196PG与LvSrc64B相结合，而其与LvSTAT互作区域为IE1C端(80-188aa)和LvSTAT N端结构域(NTD,1-130aa)。与此同时，本项目研究还发现，IE1还可促进DNA复制，并抑制血细胞凋亡和酚氧化酶活性。所获研究成果深入了解WSSV与对虾的互作机制奠定了良好的基础，同时为WSSV的防治提供了新的思路和科学依据。