The favorable IFNL3 genotype escapes mRNA decay mediated by AU-rich elements and hepatitis C virus-induced microRNAs
| Autor: | Bruce A. Shapiro, Stacy M. Horner, Curt H. Hagedorn, Rochelle C Joslyn, Mary Carrington, Michael Gale, Ram Savan, Adelle P. McFarland, Eckart Bindewald, Don A. Delker, Abigail Jarret |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Untranslated region
Genotype Hepatitis C virus RNA Stability Immunology Molecular Sequence Data Hepacivirus Biology medicine.disease_cause Polymorphism Single Nucleotide Article 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Sequence Homology Nucleic Acid microRNA medicine Immunology and Allergy Humans Psychological repression 3' Untranslated Regions 030304 developmental biology Genetic association AU-rich element AU Rich Elements 0303 health sciences Messenger RNA Base Sequence Reverse Transcriptase Polymerase Chain Reaction Interleukins Liver Neoplasms Hep G2 Cells Flow Cytometry Virology Molecular biology Hepatitis C 3. Good health MicroRNAs Host-Pathogen Interactions 030211 gastroenterology & hepatology Interferons |
| Zdroj: | Nature immunology |
| ISSN: | 1529-2916 |
| Popis: | IFNL3, which encodes interferon-l3 (IFN-l3), has received considerable attention in the hepatitis C virus (HCV) field, as many independent genome-wide association studies have identified a strong association between polymorphisms near IFNL3 and clearance of HCV. However, the mechanism underlying this association has remained elusive. In this study, we report the identification of a functional polymorphism (rs4803217) in the 3′ untranslated region (UTR) of IFNL3 mRNA that dictated transcript stability. We found that this polymorphism influenced AU-rich element (ARE)-mediated decay (AMD) of IFNL3 mRNA, as well as the binding of HCV-induced microRNAs during infection. Together these pathways mediated robust repression of the unfavorable IFNL3 polymorphism. Our data reveal a previously unknown mechanism by which HCV attenuates the antiviral response and indicate new potential therapeutic targets for HCV treatment. A r t i c l e s |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|