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IFITM1 is a tight junction protein that inhibits hepatitis C virus entry
Author(s) -
Wilkins Courtney,
Woodward Jessica,
Lau Daryl T.Y.,
Barnes Amy,
Joyce Michael,
McFarlane Nicola,
McKeating Jane A.,
Tyrrell D. Lorne,
Gale Michael
Publication year - 2013
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.26066
Subject(s) - hepatitis c virus , interferon , effector , hepatology , occludin , virology , hepatitis c , transmembrane protein , biology , virus , hepacivirus , immunology , cd81 , medicine , tight junction , receptor , microbiology and biotechnology , genetics
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. Conclusion: 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. (H EPATOLOGY 2013)