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ISG15 blocks CoxsackieB virus infection and pathology by metabolic and antiviral reprogramming

ABSTRACT: ISG15 is a ubiquitin-like modifier strongly upregulated in the type I interferon response. It exerts an antiviral function in the host defense against a wide variety of viruses. Recently, we observed that ISG15 expression restricts coxsackievirusB3 (CV) infection both in vitro and in vivo. ISG15-dependent protection against CV infection is concordant with a robust increase of ISGylated proteins in the liver of infected mice. In this study, we examined the role of ISG15 in the regulation of liver proteins at multiple stages of CV infection. To do so, we used shotgun proteomics to quantify the expression levels of the proteins from the liver tissues of wild-type and ISG15-/- mice non-infected and at day 3 and 8 of CV-infection. Our data revealed minor effects of ISG15 on the expression levels of proteins involved in the innate immune response to CV infection. In contrast, ISG15 mediates the regulation of proteins required for liver metabolic processes throughout the course of CV infection. In addition to its direct antiviral properties, our data suggest a critical role for ISG15 in rewiring liver metabolism during CV infection.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Coxsackievirus Mus Musculus (mouse)

TISSUE(S): Liver

SUBMITTER: Fabien Thery

LAB HEAD: Francis Impens

PROVIDER: PXD013259 | Pride | 2019-12-09

REPOSITORIES: Pride

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