title: IFITM1 is a tight junction protein that inhibits hepatitis C virus entry.
abstract: Type 1 interferon (IFN) continues to be the foundation for the current standard of care combination therapy for chronic hepatitis C virus (HCV) infection, yet the component interferon-stimulated genes (ISGs) that mediate the antiviral actions of IFN are not fully defined. Interferon-induced transmembrane protein 1 (IFITM1) is an ISG product that suppresses early stage infection by a number of viruses through an unknown mechanism of action. Moreover, the actions of IFITM1 on HCV infection are not fully elucidated. Here we identify IFITM1 as a hepatocyte tight junction protein and a potent anti-HCV effector molecule. IFITM1 expression is induced early during IFN treatment of hepatocytes and accumulates at hepatic tight junctions in HCV-infected human patient liver during IFN therapy. Additionally, we found that IFITM1 interacts with HCV coreceptors, including CD81 and occludin, to disrupt the process of viral entry. Thus, IFITM1 is an anti-HCV ISG whose actions impart control of HCV infection through interruption of viral coreceptor function.
  
  
  CONCLUSIONS
  This study defines IFITM1 as an ISG effector with action against HCV entry. Design of therapy regimens to enhance IFITM1 expression should improve the virologic response among HCV patients undergoing treatment with type I IFN.
authors.affiliation: Department of Immunology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Courtney
authors.initials: C
authors.lastname: Wilkins
authors.forename: Jessica
authors.initials: J
authors.lastname: Woodward
authors.forename: Daryl T-Y
authors.initials: DT
authors.lastname: Lau
authors.forename: Amy
authors.initials: A
authors.lastname: Barnes
authors.forename: Michael
authors.initials: M
authors.lastname: Joyce
authors.forename: Nicola
authors.initials: N
authors.lastname: McFarlane
authors.forename: Jane A
authors.initials: JA
authors.lastname: McKeating
authors.forename: D Lorne
authors.initials: DL
authors.lastname: Tyrrell
authors.forename: Michael
authors.initials: M
authors.lastname: Gale
mesh_terms: D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000378:metabolism / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D016174:Hepacivirus / Q000187:drug effects / Q000502:physiology; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use*; D011991:Receptors, Virus / Q000187:drug effects*; D060225:Tetraspanin 28 / Q000378:metabolism; D062725:Tight Junction Proteins / Q000502:physiology*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000943:Antigens, Differentiation; D000998:Antiviral Agents; D007370:Interferon Type I; D011991:Receptors, Virus; D060225:Tetraspanin 28; D062725:Tight Junction Proteins; C062010:leu-13 antigen