| Autor: |
Hu, Penghui, Li, Huiyi, Ji, Zemin, Jing, Weijia, Li, Zihan, Yu, Sujun, Shan, Xiao, Cui, Yan, Wang, Baochen, Dong, Hongyuan, Zhou, Yanzhao, Wang, Zhe, Xiong, Hui, Zhang, Xiaomei, Li, Hui-chieh, Wang, Jinrong, Tang, Jiuzhou, Wang, Ting, Xie, Keliang, Liu, Yuping |
| Zdroj: |
PLoS Pathogens; 12/18/2024, Vol. 20 Issue 12, p1-26, 26p |
| Abstrakt: |
Fructose-1,6-diphosphate (FBP), a key glycolytic metabolite, is recognized for its cytoprotective effects during stress. However, the role of FBP in viral infections is unknown. Here, we demonstrate that virus-infected cells exhibit elevated FBP levels. Exogenous FBP inhibits both RNA and DNA virus infections in vitro and in vivo. Modulating intracellular FBP levels by regulating the expression of the metabolic enzymes FBP1 and PFK1 significantly impacts viral infections. Mechanistically, the inhibitory effects of FBP are not a result of altered viral adhesion or entry and are largely independent of type I interferon-mediated immune responses; rather, they occur through modulation of HMGB1. During viral infections, FBP predominantly reduces the protein levels of HMGB1 by facilitating its lysosomal degradation. Furthermore, FBP interacts with HMGB1 and disrupts the binding of HMGB1 to viral genomes, thereby further inhibiting viral replication. Our findings underscore the potential of FBP as a therapeutic target for controlling viral infections. Author summary: Viral infectious diseases pose a significant threat to public health, leading to widespread illness, hospitalizations, and fatalities. Developing effective treatments is crucial for alleviating the burden of these diseases on individuals and communities. In this study, we uncovered a novel role for fructose-1,6-diphosphate (FBP), a glycolytic metabolite, in suppressing viral replication. FBP achieves this by promoting the lysosomal degradation of HMGB1 and interacting with HMGB1 to prevent its binding to the viral genome. Due to its well-documented cytoprotective effects during periods of stress, FBP has been utilized as a supplemental treatment in various countries for heart and brain conditions associated with oxygen deprivation or compromised blood supply. Our findings suggest a promising new therapeutic strategy for treating viral infectious diseases through the repurposing of FBP. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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