PMI-controlled mannose metabolism and glycosylation determines tissue tolerance and virus fitness
© 2024. The Author(s)..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
|---|---|
| Enthalten in: |
Nature communications - 15(2024), 1 vom: 08. März, Seite 2144 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Liang, Ronghui [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Antiviral Agents |
|---|
| Anmerkungen: |
Date Completed 11.03.2024 Date Revised 12.03.2024 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41467-024-46415-4 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM369487532 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM369487532 | ||
| 003 | DE-627 | ||
| 005 | 20240312234117.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240309s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41467-024-46415-4 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1324.xml |
| 035 | |a (DE-627)NLM369487532 | ||
| 035 | |a (NLM)38459021 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Liang, Ronghui |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a PMI-controlled mannose metabolism and glycosylation determines tissue tolerance and virus fitness |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 11.03.2024 | ||
| 500 | |a Date Revised 12.03.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Mannose-6-Phosphate Isomerase |2 NLM | |
| 650 | 7 | |a EC 5.3.1.8 |2 NLM | |
| 650 | 7 | |a Mannose |2 NLM | |
| 650 | 7 | |a PHA4727WTP |2 NLM | |
| 650 | 7 | |a Glucose |2 NLM | |
| 650 | 7 | |a IY9XDZ35W2 |2 NLM | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 700 | 1 | |a Ye, Zi-Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Qin, Zhenzhi |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Yubin |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Xiaomeng |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Haoran |e verfasserin |4 aut | |
| 700 | 1 | |a Du, Qiaohui |e verfasserin |4 aut | |
| 700 | 1 | |a Luo, Peng |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Kaiming |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Bodan |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Jianli |e verfasserin |4 aut | |
| 700 | 1 | |a Wong, Xavier Hoi-Leong |e verfasserin |4 aut | |
| 700 | 1 | |a Ling, Guang-Sheng |e verfasserin |4 aut | |
| 700 | 1 | |a Chu, Hin |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Jiangang |e verfasserin |4 aut | |
| 700 | 1 | |a Yin, Feifei |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Dong-Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Jasper Fuk-Woo |e verfasserin |4 aut | |
| 700 | 1 | |a Yuen, Kwok-Yung |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Shuofeng |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nature communications |d 2010 |g 15(2024), 1 vom: 08. März, Seite 2144 |w (DE-627)NLM199274525 |x 2041-1723 |7 nnns |
| 773 | 1 | 8 | |g volume:15 |g year:2024 |g number:1 |g day:08 |g month:03 |g pages:2144 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41467-024-46415-4 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 15 |j 2024 |e 1 |b 08 |c 03 |h 2144 | ||