Fructose-1,6-diphosphate inhibits viral replication by promoting the lysosomal degradation of HMGB1 and blocking the binding of HMGB1 to the viral genome

被引：0

作者：

Hu, Penghui ^{[1
]}

Li, Huiyi ^{[2
]}

Ji, Zemin ^{[3
]}

Jing, Weijia ^{[3
]}

Li, Zihan ^{[3
]}

Yu, Sujun ^{[3
]}

Shan, Xiao ^{[4
,5
]}

Cui, Yan ^{[3
]}

Wang, Baochen ^{[3
]}

Dong, Hongyuan ^{[3
]}

Zhou, Yanzhao ^{[6
,7
,8
]}

Wang, Zhe ^{[4
,5
]}

Xiong, Hui ^{[3
]}

Zhang, Xiaomei ^{[4
,5
]}

Li, Hui-chieh ^{[4
,5
]}

Wang, Jinrong ^{[3
]}

Tang, Jiuzhou ^{[3
]}

Wang, Ting ^{[9
,10
]}

Xie, Keliang ^{[11
]}

Liu, Yuping ^{[4
,5
]}

Zhu, Haizhen ^{[2
]}

Yu, Qiujing ^{[4
,5
]}

机构：

[1] Tianjin Med Univ, Gen Hosp, Tianjin Inst Immunol, Sch Basic Med Sci,Minist Educ,Dept Immunol,Dept Cr, Tianjin, Peoples R China

[2] Hainan Med Univ, Affiliated Hosp 2, Univ Hong Kong Joint Lab Trop Infect Dis, Sch Basic Med & Life Sci,Minist Educ,Dept Pathogen, Hainan, Peoples R China

[3] Tianjin Med Univ, Tianjin Inst Immunol, Sch Basic Med Sci, Dept Immunol,Minist Educ,State Key Lab Expt Hemato, Tianjin, Peoples R China

[4] Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Dept Hlth Management Ctr, Chengdu, Peoples R China

[5] Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Inst Hlth Management, Chengdu, Peoples R China

[6] Zhengzhou Univ, Affiliated Canc Hosp, Dept Med Oncol, Zhengzhou, Peoples R China

[7] Henan Canc Hosp, Zhengzhou, Peoples R China

[8] Univ Elect Sci & Technol China, Chengdu, Peoples R China

[9] Tianjin Med Univ, Prov & Minist Cosponsored Collaborat Innovat Ctr M, Sch Basic Med Sci, Dept Pharmacol, Tianjin, Peoples R China

[10] Tianjin Med Univ, Tianjin Key Lab Inflammat Biol, Tianjin, Peoples R China

[11] Tianjin Med Univ, Gen Hosp, Tianjin Inst Anesthesiol, Dept Crit Care Med,Dept Anesthesiol, Tianjin, Peoples R China

来源：

PLOS PATHOGENS | 2024年 / 20卷 / 12期

基金：

中国国家自然科学基金;

关键词：

GROUP BOX 1; INNATE IMMUNITY; VIRUS-INFECTION; PROTEIN; HOST; FRUCTOSE-1,6-BISPHOSPHATE; RELEASE; METABOLISM;

D O I：

10.1371/journal.ppat.1012782

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页数：26

共 41 条

[41] Tandem mass tag (TMT) labeling-based quantitative proteomic analysis reveals the cellular protein characteristics of 16HBE cells infected with coxsackievirus A10 and the potential effect of HMGB1 on viral replication
Song, Jie
Zhao, Guifang
Li, Hui
Yang, Yan
Yu, Yue
Hu, Yunguang
Li, Yadong
Li, Jiang
Hu, Yajie
ARCHIVES OF VIROLOGY, 2023, 168 (08)

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