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Cell Rep. 2016 Oct 25;17(5):1357-1368. doi: 10.1016/j.celrep.2016.09.084.

Solute Carrier NTCP Regulates Innate Antiviral Immune Responses Targeting Hepatitis C Virus Infection of Hepatocytes.

Author information

1
INSERM, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, 67000 Strasbourg, France; Université de Strasbourg, 67000 Strasbourg, France.
2
INTS, Laboratoire de Virologie Moléculaire, 75015 Paris, France.
3
CIRI-International Center for Infectiology Research, 69364 Lyon Cedex 07, France; INSERM, U1111, 69007 Lyon, France; Ecole Normale Supérieure, 69007 Lyon, France; Centre National de la Recherche Scientifique (CNRS) UMR 5308, 69007 Lyon, France; LabEx Ecofect, University of Lyon, 69007 Lyon, France.
4
Centre for Human Virology, University of Birmingham, Birmingham, UK; NIHR Liver Biomedical Research Unit, University of Birmingham, Birmingham, UK.
5
INSERM, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, 67000 Strasbourg, France; Université de Strasbourg, 67000 Strasbourg, France; Institut Hospitalo-universitaire, Pôle Hépato-digestif, Nouvel Hôpital Civil, 67000 Strasbourg, France.
6
Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Liver Cancer Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
7
INSERM, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, 67000 Strasbourg, France; Université de Strasbourg, 67000 Strasbourg, France. Electronic address: mirjam.zeisel@unistra.fr.
8
INSERM, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, 67000 Strasbourg, France; Université de Strasbourg, 67000 Strasbourg, France; Institut Hospitalo-universitaire, Pôle Hépato-digestif, Nouvel Hôpital Civil, 67000 Strasbourg, France. Electronic address: thomas.baumert@unistra.fr.

Abstract

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.

KEYWORDS:

NTCP; antiviral therapy; hepatitis B virus; hepatitis C virus; hepatitis D virus; host factor; innate immune responses; signaling; solute carrier; viral entry

PMID:
27783949
PMCID:
PMC5098118
DOI:
10.1016/j.celrep.2016.09.084
[Indexed for MEDLINE]
Free PMC Article

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