Hepatic IFN-Induced Protein with Tetratricopeptide Repeats Regulation of HCV Infection

Abstract

Interferons (IFNs) suppress viral infection through the induction of >400 interferon-stimulated genes (ISGs). Among ISGs, IFN-induced protein with tetratricopeptide repeats (IFITs) is one of the most potent and wellcharacterized ISGs. IFIT family consists of 4 cluster genes. It has been suggested that the antiviral action of each IFIT employs distinct mechanisms. In addition, it has been shown that each IFIT exhibits its antiviral properties partially in a pathogen-specific manner. To date, the expression profile of IFITs in the liver, as well as the antiviral potency of the individual IFITs in the regulation of hepatitis C virus (HCV) infection, is not yet fully defined. Our previous study found that the expression of hepatic IFITs is well correlated with the outcome of IFN-based antiviral therapy. This study explored the significance of each IFIT in the suppression of HCV. Our in vitro and in vivo studies with humanized liver chimeric mouse system revealed that IFIT1, 2, and 3/4 play an important role in the suppression of HCV. In addition, our in vitro experiment found that all IFITs possess a comparable anti-HCV potency. Follow-up studies collectively indicated that IFITs suppress HCV likely through 2 distinct mechanisms: (1) inhibition of internal ribosome entry site-dependent viral protein translation initiation complex according to experiments with bicistronic reporter assay as well as confocal

Exploring the comorbidity mechanisms between psoriasis and obesity based on bioinformatics

“…In addition, IFIT is a class of proteins induced by large amounts of IFN produced by the interferon‐stimulated gene family (ISG) in response to invasion by viruses and other pathogens, through Toll‐like receptor signaling pathways, NF‐κB signaling pathways, and JAK/STAT signaling pathways, with IRF9 playing a crucial role in this process. IFIT1, IFIT3, and others can further promote the production of more IFN 24–27 . Considering that the genes involved in this study are closely related to Toll‐like receptor signaling pathways, NF‐κB signaling pathways, IFN, etc., it can be seen that there is a close connection between psoriasis, obesity, and nonalcoholic steatohepatitis.…”

Galectin-9 and Interferon-Gamma Are Released by Natural Killer Cells upon Activation with Interferon-Alpha and Orchestrate the Suppression of Hepatitis C Virus Infection

“…Both proteins are involved in the antiviral response mounted by host cells and are dependent on IFN signaling [ 65 ]. In particular, IFIT1 inhibits HCV replication by blocking internal ribosome entry site (IRES)-dependent translation [ 66 ]. The MX1 protein is a GTPase that acts in the early step of the viral life cycle by blocking the endocytic traffic of incoming virus particles and preventing them from reaching their cellular destination [ 67 , 68 ].…”

Transcriptome analysis of PK-15 cells expressing CSFV NS4A

“…Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) inhibits virus replication and translation initiation. Upregulation of the IFIT1 gene is closely linked to the replication inhibition of many viruses, including hepatitis E virus and hepatitis C virus (HCV) [ 22 , 23 ]. 2’-5’-Oligoadenylate synthetase 1 (OAS1) activates latent RNase L, which results in viral RNA degradation and inhibition of virus replication and mediates the antiviral effect against HCV, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and dengue virus (DENV) [ 24 – 26 ].…”