Fructose-1,6-diphosphate inhibits viral replication by promoting the lysosomal degradation of HMGB1 and blocking the binding of HMGB1 to the viral genome
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.
Authors
- Haizhen Zhu (ORCID: https://orcid.org/0000-0001-5926-6186)
- Qiujing Yu (ORCID: https://orcid.org/0000-0002-3978-643X)
- Hui-chieh Li
- Hui Xiong (ORCID: https://orcid.org/0000-0002-2110-6002)
- Zemin Ji
- Sujun Yu
- Penghui Hu (ORCID: https://orcid.org/0000-0003-3876-2732)
- Xiaomei Zhang (ORCID: https://orcid.org/0000-0002-8545-0283)
- Ting Wang (ORCID: https://orcid.org/0000-0003-2257-0699)
- Weijia Jing
- Zihan Li (ORCID: https://orcid.org/0009-0001-1334-027X)
- Yuping Liu (ORCID: https://orcid.org/0000-0001-8053-0826)
- Yan Cui (ORCID: https://orcid.org/0000-0002-5880-7275)
- Jinrong Wang (ORCID: https://orcid.org/0000-0002-1963-1764)
- Yanzhao Zhou (ORCID: https://orcid.org/0000-0002-4784-3596)
- Huiyi Li (ORCID: https://orcid.org/0000-0001-9574-7251)
- Keliang Xie (ORCID: https://orcid.org/0000-0001-6362-6084)
- Hongyuan Dong (ORCID: https://orcid.org/0009-0008-9008-4282)
- Baochen Wang
- Xiao Shan
- Jiuzhou Tang
- Zhe Wang (ORCID: https://orcid.org/0000-0003-0786-9887)
Institutions
- University of Electronic Science and Technology of China (CN)
- Tianjin Medical University General Hospital (CN)
- Zhengzhou University (CN)
- Henan Cancer Hospital (CN)
- Tianjin Medical University (CN)
- Hainan Medical University (CN)
- University of Hong Kong (HK)
Publication Details
- Journal
- PLoS Pathogens
- Published
- 2024-12-18
- DOI
- https://doi.org/10.1371/journal.ppat.1012782
- Citations
- 2
- Primary Topic
- Advanced Glycation End Products research
- Type
- article
- Field-Weighted Citation Impact
- 0.76
Funders
- Yale University
- National Natural Science Foundation of China
- Soochow University