猪瘟病毒调控糖酵解关键酶─乳酸脱氢酶B的作用机制研究

猪瘟是由猪瘟病毒引起的猪急性传染病，给养猪业造成巨大的经济损失。猪瘟病毒感染引起机体免疫抑制和代谢紊乱，是其持续感染宿主的主要原因。我们前期研究发现，猪瘟病毒感染造成糖酵解代谢进程紊乱，并抑制糖酵解关键调控酶─乳酸脱氢酶B的表达，这不仅促进病毒自身复制，而且引起糖酵解代谢终产物乳酸的积累。然而，猪瘟病毒调控乳酸脱氢酶B的机制和乳酸积累的分子效应尚不清楚。基于此，本项目将采用细胞生物学和病毒学的方法，明确猪瘟病毒与乳酸脱氢酶B的相互调控作用。在已有工作基础上，研究E3泛素连接酶在猪瘟病毒调控乳酸脱氢酶B中的分子机制。进一步探索猪瘟病毒引起的乳酸积累通过乳酸脱氢酶B和抗病毒蛋白MAVS“交互对话”作用于病毒复制的机制。研究成果将揭示猪瘟病毒通过调控乳酸脱氢酶B促进自身复制的完整链条，进而从新的角度阐明猪瘟病毒持续感染的机制，为筛选抗猪瘟病毒靶点和猪瘟防控提供科学依据。

Classical swine fever virus (CSFV) is the etiological agent of classical swine fever (CSF) and causes high morbidity and mortality rates in piglets, leading to major economic losses for swine farms. CSFV has evolved mechanisms that induce immunosuppression and rebuild metabolic programs, and is, therefore, able to establish persistent infection. Our previous research found that CSFV infection serves a disorder and rebuilding of glycolysis, and inhibits the expression of lactate dehydrogenase B (LDHB), a key regulatory glycolysis enzyme. Inhibition of LDHB is not only facilitates the replication of CSFV, but also promotes the production of lactate, the end product of glycolysis. However, the underlying mechanisms used by CSFV to inhibit LDHB and the mechanism by which lactate regulates viral replication remain unclear. On this basis, the project will apply the methods of cell biology and virology to distinct the mutual regulation between CSFV and LDHB. Furthermore, we plan to explore the function of E3 ubiquitin ligase in CSFV regulating LDHB, as well as reveal the approaches of lactate in CSFV replication through the crosstalk between antiviral protein MAVS and LDHB. The project aimed to further uncover the underlying mechanism of CSFV exploiting LDHB, and clarify the reason of CSFV persistent infection from a new perspective. This work will provide scientific avenues for screening anti- CSFV targets and control strategies for CSF.