Solute Carrier NTCP Regulates Innate Antiviral Immune Responses Targeting Hepatitis C Virus Infection of Hepatocytes.
Fiche publication
Date publication
octobre 2016
Journal
Cell reports
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BAUMERT Thomas, Pr PESSAUX Patrick, Dr CROUCHET Emilie, Dr VERRIER Eloi
Tous les auteurs :
Verrier ER, Colpitts CC, Bach C, Heydmann L, Zona L, Xiao F, Thumann C, Crouchet E, Gaudin R, Sureau C, Cosset FL, McKeating JA, Pessaux P, Hoshida Y, Schuster C, Zeisel MB, Baumert TF
Lien Pubmed
Résumé
Chronic hepatitis B, C, and D virus (HBV, HCV, and HDV) infections are the leading causes of liver disease and cancer worldwide. Recently, the solute carrier and sodium taurocholate co-transporter NTCP has been identified as a receptor for HBV and HDV. Here, we uncover NTCP as a host factor regulating HCV infection. Using gain- and loss-of-function studies, we show that NTCP mediates HCV infection of hepatocytes and is relevant for cell-to-cell transmission. NTCP regulates HCV infection by augmenting the bile-acid-mediated repression of interferon-stimulated genes (ISGs), including IFITM3. In conclusion, our results uncover NTCP as a mediator of innate antiviral immune responses in the liver, and they establish a role for NTCP in the infection process of multiple viruses via distinct mechanisms. Collectively, our findings suggest a role for solute carriers in the regulation of innate antiviral responses, and they have potential implications for virus-host interactions and antiviral therapies.
Référence
Cell Rep. 2016 Oct;17(5):1357-1368