TIPE1 limits virus replication by disrupting PKM2/ HIF-1α/ glycolysis feedback loop

Area of Science:

• Immunology
• Virology
• Cellular Metabolism

Background:

• Virus infections pose significant health risks, with macrophages playing a crucial role in innate immunity against viral replication.
• Metabolic adaptation is critical for macrophage function, suggesting that understanding these adaptations can enhance antiviral strategies.

Purpose of the Study:

• To investigate the role of TIPE1 in macrophage metabolic reprogramming during virus infection.
• To identify potential therapeutic targets for optimizing macrophage antiviral capabilities.

Main Methods:

• Quantitative reverse transcription PCR (RT-PCR), Western blotting, virus plaque assays, and hematoxylin and eosin (HE) staining were used to assess viral loads.
• RNA sequencing, extracellular acidification rate (ECAR) analysis, co-immunoprecipitation (Co-IP), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were employed to investigate molecular mechanisms.

Main Results:

• TIPE1 levels decreased in macrophages infected with RNA or DNA viruses.
• TIPE1 deficiency led to increased viral load and exacerbated tissue damage.
• TIPE1 interacts with PKM2, promoting its ubiquitination and degradation, which suppresses macrophage glycolysis and HIF1α transcription, thereby inhibiting viral replication.

Conclusions:

• TIPE1 acts as a novel regulator of metabolic reprogramming in macrophages during viral infections.
• Targeting TIPE1 may offer a strategy to enhance macrophage antiviral responses.