Autophagy-to-Apoptosis Conversion Mediated by GIMAP7 Exhibit Anti-RSV Action

RSV is a notable respiratory pathogen. GIMAP7, an essential member of the immune protein family, might mitigate RSV infection. The aim of this project is to determine GIMAP7's function during RSV infection and evolve drugs targeting it. Employing Bioinformatics, immunoprecipitation, RT-qPCR, and Western blot to scrutinize the outcome of GIMAP7 overexpression on RSV-induced incomplete to complete autophagy, apoptosis activation, and RSV replication restriction. Computer-aided screening was utilized to screen GIMAP7 agonists. Predominantly expressed in the lung, GIMAP7 resides within membranous organelles like the Golgi apparatus, endoplasmic reticulum, and lysosomes. RSV infection triggers incomplete autophagy flux that utilizes autophagosomes as its replication niche. Direct GIMAP7-LC3B interaction converts RSV-induced incomplete autophagy into complete autophagy, inciting apoptosis and reducing RSV replication. Narirutin and Periplocin markedly activate GIMAP7 expression in vivo and in vitro, stimulating complete autophagy flux and apoptosis. The study exhibits the novel role of GIMAP7 in converting incomplete to complete autophagy and the identification of narirutin/periplocin as GIMAP7 agonists.