I型干扰素（IFN-I）及其诱导的干扰素刺激基因（ISGs）是抗病毒免疫的核心。多种代谢关键酶在病毒感染的细胞中表达上调，这些酶在抗病毒免疫中的作用尚不明确。我们通过分析病毒感染细胞和IFN-I活化细胞的转录组，发现糖酵解关键酶PFKFB3也是ISG，可以通过酶活依赖的方式促进宿主抗病毒免疫，保护HEK293T等细胞抵抗多种病毒感染。此外，PFKFB3的条件培养基能通过IFNAR非依赖的方式活化STAT1，从而促进抗病毒基因的诱导表达。利用代谢组学、补充营养成分等实验初步证明PFKFB3条件培养基能通过消耗代谢物的方式使其具有抗病毒的能力。本项目将研究PFKFB3及其条件培养基在宿主抗病毒免疫中的调控作用、阐明PFKFB3条件培养基具有抗病毒活性的原因、探讨PFKFB3及其条件培养基以IFNAR非依赖的方式活化STAT1的分子机制，从而为寨卡、流感等病毒感染性疾病的防治提供新的靶点和策略。

Type I interferon (IFN-I) plays critical roles in host antiviral immunity by inducing numerous antiviral IFN-stimulated genes (ISGs) through the IFNAR downstream signaling. Induction of some metabolic key enzymes and their metabolites was also observed in the viral-infected cells. However, it is unclear whether these enzymes regulate host antiviral immunity. By analyzing the transcriptome of the viral-infected or IFN-I-treated cells, we have found that glycolytic activator 6-phosphofructose-2-kinase and fructose-2,6-bisphosphatase (PFKFB3) is also an ISG. PFKFB3 protects HEK293T and A549 cells against viral infection in an enzymatic activity-dependent manner. In addition, the conditional medium from PFKFB3-overexpressed HEK293T cells (CM-PFKFB3) facilitates STAT1 phosphorylation and antiviral ISGs induction via an IFNAR-independent pathway. By using HPLC-MS/MS analyzing the metabolomics in CM-PFKFB3 and testing the effect of the differential produced metabolites, the results suggest that PFKFB3 enhances host antiviral immunity by depleting one or more metabolites, such as amino acids. In this project, we will further investigate the role of PFKFB3 and CM-PFKFB3 in the regulation of host antiviral immunity, the reason for the antiviral activity of CM-PFKFB3, the mechanism for PFKFB3 and CM-PFKFB3 promoting activation of STAT1. This study will provide novel therapeutic targets and strategies for treatment of viral infectious diseases caused by ZIKV, influenza, and herpes virus infection.