The IRG1-Itaconate Axis Promotes Viral Replication Via Metabolic Reprogramming and Protein Prenylation

Itaconate is a product of immune responsive gene 1 (IRG1) and an important immune-activated metabolic enzyme. Previous studies indicated that IRG1-itaconate may reprogram cell metabolism, and is involved in the regulation of inflammatory responses and anti-bacterial immunity. However, its role in viral infection and the mechanisms involved remain unclear. Here, we found that the IRG1-itaconate axis is required for the effective infection of macrophages and epithelial cells by virus via an IFN-I independent mechanism. Further studies revealed that isoprenoid and protein prenylation are responsible for this IRG1-itaconate-mediated viral overgrowth. These findings demonstrate a critical role of the IRG1-itaconate axis in viral infection and provide potential targets for developing antiviral therapeutics.