Transcriptomics

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


ABSTRACT: This study explored the regulatory effect of D-mannose on host immunometabolic responses after viral infection. The results showed that D-mannose can compete with glucose for transporters and hexokinase, inhibiting glycolysis, reducing mitochondrial reactive oxygen species and succinate-induced HIF-1α, thereby reducing virus-induced inflammatory cytokine production. Even with delayed combinatorial treatment of D-mannose and antiviral monotherapy after viral infection, a synergistic effect was still observed in mouse models. Phosphomannose isomerase (PMI) activity determines the benefits of D-mannose, as simultaneous PMI depletion and mannose supplementation impaired cell viability. PMI inhibition can suppress replication of various viruses by affecting host and viral surface protein glycosylation. However, D-mannose does not inhibit PMI activity or viral fitness. In summary, PMI-centered therapeutic strategies can eliminate viral infections, while D-mannose treatment reprograms glycolysis to control collateral damage.

ORGANISM(S): Homo sapiens

PROVIDER: GSE255332 | GEO | 2024/02/13

REPOSITORIES: GEO

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