PMI-controlled mannose metabolism and glycosylation determines tissue tolerance and virus fitness

Ronghui Liang, Zi Wei Ye, Zhenzhi Qin, Yubin Xie, Xiaomeng Yang, Haoran Sun, Qiaohui Du, Peng Luo, Kaiming Tang, Bodan Hu, Jianli Cao, Hoi Leong Xavier Wong, Guang-Sheng Ling, Hin Chu, Jiangang Shen, Feifei Yin, Dong Yan Jin, Jasper Fuk-Woo Chan, Kwok-Yung Yuen, Shuofeng Yuan*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

Abstract

Host survival depends on the elimination of virus and mitigation of tissue damage. Herein, we report the modulation of D-mannose flux rewires the virus-triggered immunometabolic response cascade and reduces tissue damage. Safe and inexpensive D-mannose can compete with glucose for the same transporter and hexokinase. Such competitions suppress glycolysis, reduce mitochondrial reactive-oxygen-species and succinate-mediated hypoxia-inducible factor-1α, and thus reduce virus-induced proinflammatory cytokine production. The combinatorial treatment by D-mannose and antiviral monotherapy exhibits in vivo synergy despite delayed antiviral treatment in mouse model of virus infections. Phosphomannose isomerase (PMI) knockout cells are viable, whereas addition of D-mannose to the PMI knockout cells blocks cell proliferation, indicating that PMI activity determines the beneficial effect of D-mannose. PMI inhibition suppress a panel of virus replication via affecting host and viral surface protein glycosylation. However, D-mannose does not suppress PMI activity or virus fitness. Taken together, PMI-centered therapeutic strategy clears virus infection while D-mannose treatment reprograms glycolysis for control of collateral damage.
Original languageEnglish
Article number2144
Number of pages15
JournalNature Communications
Volume15
Issue number1
DOIs
Publication statusPublished - 8 Mar 2024

Scopus Subject Areas

  • Physics and Astronomy(all)
  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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