Hepatic IFN-Induced Protein with Tetratricopeptide Repeats Regulation of HCV Infection
| Autor: | Michael Gale, Takeshi Saito, Daryl T.-Y. Lau, Bo-Ram Bang, Go Sugahara, Meng Li, Masakazu Kakuni, Chise Tateno-Mukaidani, Yuji Ishida |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Reporter gene Viral protein Hepatitis C virus Immunology Research Reports Cell Biology Biology medicine.disease_cause Virology In vitro 03 medical and health sciences Tetratricopeptide 030104 developmental biology 0302 clinical medicine In vivo medicine 030211 gastroenterology & hepatology Translation initiation complex Gene |
| Zdroj: | Journal of Interferon & Cytokine Research. 39:133-146 |
| ISSN: | 1557-7465 1079-9907 |
| DOI: | 10.1089/jir.2018.0103 |
| Popis: | 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 well-characterized 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 microscopic analyses and (2) sequestration of viral genome based on an experiment using replication defective viral genome. In conclusion, our study defined the importance of IFITs in the regulation of HCV and also suggested the multifaceted antiviral actions. |
| Databáze: | OpenAIRE |
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