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

54 Pages Posted: 22 Aug 2019 Sneak Peek Status: Under Review

See all articles by Shulei Yin

Shulei Yin

Second Military Medical University - National Key Laboratory of Medical Immunology & Institute of Immunology

Dan Han

Second Military Medical University - National Key Laboratory of Medical Immunology & Institute of Immunology

Yijie Tao

Second Military Medical University - National Key Laboratory of Medical Immunology & Institute of Immunology

Sheng Xu

Second Military Medical University - National Key Laboratory of Medical Immunology & Institute of Immunology

Tianliang Li

Second Military Medical University - National Key Laboratory of Medical Immunology & Institute of Immunology

Jiangxue Li

Zhejiang University - Institute of Immunology

Yingke Li

Second Military Medical University - National Key Laboratory of Medical Immunology & Institute of Immunology

Jingyi Huang

Second Military Medical University - National Key Laboratory of Medical Immunology & Institute of Immunology

Xuetao Cao

Second Military Medical University - National Key Laboratory of Medical Immunology & Institute of Immunology

Yizhi Yu

Second Military Medical University - National Key Laboratory of Medical Immunology & Institute of Immunology

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Abstract

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

Suggested Citation

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). CELL-METABOLISM-D-19-00910. Available at SSRN: https://ssrn.com/abstract=3440261 or http://dx.doi.org/10.2139/ssrn.3440261
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Shulei Yin

Second Military Medical University - National Key Laboratory of Medical Immunology & Institute of Immunology ( email )

Shanghai, 200433
China

Dan Han

Second Military Medical University - National Key Laboratory of Medical Immunology & Institute of Immunology

Shanghai, 200433
China

Yijie Tao

Second Military Medical University - National Key Laboratory of Medical Immunology & Institute of Immunology ( email )

Shanghai, 200433
China

Sheng Xu

Second Military Medical University - National Key Laboratory of Medical Immunology & Institute of Immunology

Shanghai, 200433
China

Tianliang Li

Second Military Medical University - National Key Laboratory of Medical Immunology & Institute of Immunology ( email )

Shanghai, 200433
China

Jiangxue Li

Zhejiang University - Institute of Immunology ( email )

Hangzhou, 310058
China

Yingke Li

Second Military Medical University - National Key Laboratory of Medical Immunology & Institute of Immunology ( email )

Shanghai, 200433
China

Jingyi Huang

Second Military Medical University - National Key Laboratory of Medical Immunology & Institute of Immunology

Shanghai, 200433
China

Xuetao Cao

Second Military Medical University - National Key Laboratory of Medical Immunology & Institute of Immunology ( email )

Shanghai, 200433
China

Yizhi Yu (Contact Author)

Second Military Medical University - National Key Laboratory of Medical Immunology & Institute of Immunology ( email )

Shanghai, 200433
China

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