电子科技大学最新Cell：郑慧团队发现全新蛋白质修饰类型——丙酮酸化修饰，揭开高血糖降低抗病毒免疫之谜

Core Viewpoint - The research reveals a novel post-translational modification of proteins, specifically pyruvylation, which demonstrates how high glucose levels can impair antiviral immunity by inhibiting interferon signaling through the modification of the STAT1 protein [3][10][18]. Group 1: Research Findings - The study identifies pyruvate as a natural suppressor of interferon signaling, indicating that high glucose levels enhance glycolysis, leading to increased pyruvate levels that induce pyruvylation of STAT1 at lysine 201, thereby inhibiting type I interferon (IFN-I) signaling and antiviral immune activity [3][8][16]. - RNA sequencing analysis shows that under high glucose conditions, the glycolytic pathway is activated while the IFN-I signaling pathway is significantly suppressed, with pyruvate kinase M2 (PKM2) being a key inhibitory molecule [9][10]. - The research establishes a direct link between high blood sugar and reduced antiviral immunity, providing a molecular explanation for the increased susceptibility of diabetic patients to viral infections [6][15]. Group 2: Mechanism and Implications - The mechanism involves spatial hindrance caused by pyruvylation, which prevents the normal interaction between STAT1 and STAT2, essential for initiating IFN-I signaling and activating downstream antiviral gene expression [11][12]. - The study's findings suggest potential therapeutic strategies to enhance antiviral immunity in high glucose populations by targeting pyruvate metabolism or blocking STAT1 pyruvylation [16][20]. Group 3: Future Directions - Future research may focus on developing small molecules that specifically inhibit STAT1 pyruvylation, exploring the role of pyruvylation in other diseases such as autoimmune disorders and cancer, and mapping other proteins that may undergo pyruvylation [20][21].