STING exerts antiviral innate immune response by activating pentose phosphate pathway

• DOI: 10.1186/s12964-024-01983-2
• Publication Date: 2024-12-18T15:37:40Z
• Authors: Dan-Hui Wu; Zi-Long Zhao; Wei-Tao Yin; Huai Liu; Xiong-Yan Xiang; Ling-Jun Zhu; Jun-Qi Li; Zhen-Hua Yan; Yu-Jia Li; Yong-Ping Jian; Zhi-Xiang Xu
• Keywords: Antiviral immune response; PPP; QH573-671; Research; Inflammatory factors; R; Medicine; Transketolase; Cytology; STING

The innate immune system serves as the host's first line of defense against invading pathogens. Stimulator interferon genes (STING) is a key component this system, yet its relationship with glucose metabolism, particularly in antiviral immunity, remains underexplored. Metabolomics analysis was used for detecting metabolic alterations spleens from STING knockout (KO) and wild-type (WT) mice. Co-immunoprecipitation employed determining ubiquitination TKT. Mass spectrometry interaction proteins STING. Enzyme activity kits were activities TKT G6PD. In study, we demonstrate that herpes simplex virus (HSV) infection activates pentose phosphate pathway (PPP) host cells, thereby initiating an response. Using STING-manipulated cells systemic mice, show positively regulates PPP, which, turn, limits HSV infection. Inhibition PPP significantly reduced production factors dampened STING-induced responses. Mechanistically, discovered interacts transketolase (TKT), enzyme non-oxidative branch reduces via E3 ubiquitin ligase UBE3A, stabilizing Silencing or inhibiting oxythiamine diminished factor production. Our findings reveal plays synergistic role generating during viral suggest activation could serve adjunct strategy therapy.