The bittersweet link between glucose metabolism, cellular microenvironment and viral infection

Viral particles and proteins released during infection profoundly reshape the cellular microenvironment by disrupting host signaling, triggering inflammation, and modulating immune responses. Glucose metabolism, a critical hub for energy production and biosynthesis, is highly susceptible to viral reprogramming. This review summarizes recent findings showing that diverse viruses, including influenza virus, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and enteroviruses, manipulate glucose metabolic pathways to promote replication and evade immune surveillance. Specifically, viruses modulate glycolytic flux, alter the activity of key metabolic enzymes such as hexokinase (HK) and pyruvate kinase, and interfere with signaling networks like PI3K/Akt/mTOR and AMPK. These metabolic alterations further impact the immune landscape by regulating cytokine production, immune cell activation, and antiviral responses. Our analysis highlights a bidirectional interaction: while viruses hijack host glucose metabolism to favor their survival, metabolic changes also generate host-derived antiviral responses. This review highlights the bidirectional crosstalk between metabolic remodeling and microenvironmental changes during viral infection, underscoring the potential of metabolism-based antiviral strategies. A deeper understanding of these mechanisms may inform the development of more effective and targeted interventions against viral diseases.