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.
Keywords: Immune responsive gene 1, itaconate, type I interferon, viral replication, prenylation
Yin, Shulei and Han, Dan and Tao, Yijie and Xu, Sheng and Li, Tianliang and Li, Jiangxue and Li, Yingke and Huang, Jingyi and Cao, Xuetao and Yu, Yizhi, The IRG1-Itaconate Axis Promotes Viral Replication Via Metabolic Reprogramming and Protein Prenylation (August 21, 2019). Available at SSRN: https://ssrn.com/abstract=3440261 or http://dx.doi.org/10.2139/ssrn.3440261
This version of the paper has not been formally peer reviewed.
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