Topical 2-deoxy-d-glucose restores MAVS-associated antiviral signaling in herpes simplex keratitis

Herpes simplex keratitis (HSK), caused by herpes simplex virus type 1 (HSV-1), is a leading cause of infectious corneal blindness. Current antiviral therapies often face challenges due to viral immune evasion and metabolic reprogramming that impair host antiviral responses, particularly type I interferon (IFN) signaling. This study addresses the gap in understanding how HSV-1 manipulates corneal cell metabolism, specifically glycolysis, to suppress the crucial mitochondrial antiviral signaling (MAVS) pathway, and explores metabolic modulation as a novel therapeutic strategy.

Researchers established in vitro and in vivo HSV-1 McKrae infection models. A stable hexokinase 2 (HK2)-knockdown human corneal epithelial cell (HCEC) line was generated using lentivirus. Protein and mRNA levels were analyzed via western blot (WB), immunofluorescence (IF), ELISA, and real-time polymerase chain reaction (RT-PCR). Protein interactions were confirmed by co-immunoprecipitation (Co-IP). Murine corneal pathology and viral proteins were assessed by slit-lamp imaging, IF, and WB following topical application of 2-deoxy-d-glucose (2-DG). The study compared 2-DG efficacy to acyclovir.