HCV Core Protein-ISX Axis Promotes Chronic Liver Disease Progression via Metabolic Remodeling and Immune Suppression.

ABSTRACT: Chronic hepatitis C virus (HCV) infection is an important public health issue. However, knowledge on how the virus remodels the metabolic and immune response toward hepatic pathologic environment is limited. The transcriptomic and multiple evidences reveal that the HCV core protein-intestine-specific homeobox (ISX) axis promotes a spectrum of metabolic, fibrogenic, and immune modulators (e.g., kynurenine, PD-L1, and B7-2), regulating HCV-infection relevant pathogenic phenotype in vitro and in vivo. In a transgenic mice model, the HCV core protein-ISX axis enhance metabolic disturbance (particularly lipid and glucose metabolism) and immune suppression, and finally, chronic liver fibrosis in a high-fat diet (HFD)-induced disease model. Mechanistically, cells with HCV JFH-1 replicons upregula

SUBMITTER: Wang LT 

PROVIDER: S-EPMC10427408 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature