GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE298nnn/GSE298514/primary200OKTranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE298514GEOGSEfalseVanin-1 deficiency enhances host tolerance to influenza infection by modulating cellular redox statusHost survival during infection depends on the balance between pathogen resistance and tissue tolerance mechanisms. Although resistance pathways are well-characterized, the molecular determinants of host tolerance remain poorly understood. Here we demonstrate that vanin-1, an ectoenzyme known for its role in vitamin B5 metabolism, unexpectedly regulates host tolerance during influenza infection through modulation of cellular redox status. Mice lacking vanin-1 showed enhanced survival following lethal influenza infection without alterations in viral burden, immune responses, or tissue pathology. While vanin-1 deficiency impairs vitamin B5 metabolism, neither vitamin B5 supplementation nor deficiency affected survival during infection, indicating a vitamin B5- independent mechanism. RNA sequencing analysis revealed enhanced expression of antioxidant pathway genes in vanin-1-deficient mice, with Nrf2 serving as a key upstream regulator. Mechanistically, vanin-1-deficient mice maintained higher glutathione levels during infection and showed reduced lipid peroxidation, suggesting protection against oxidative stress-induced cell death. Importantly, pharmacological inhibition of glutathione synthesis abolished the survival advantage in vanin-1-deficient mice, while glutathione supplementation protected wild-type mice from lethal infection. Our findings reveal an unexpected role for vanin-1 in regulating host tolerance through antioxidant pathways and identify a potential therapeutic target for enhancing survival during severe viral infections.2026/06/22GSE298514GSM9015947GSM9015948GSM9015949GSM9015950GSM9015951GSM9015952GSM9015953GSM9015954GSM9015955GSM9015956GSM9015957GSM901594634290298514Mus musculus[42369873]