title: Interleukin 6 inhibits HBV entry through NTCP down regulation.
abstract: Hepatitis B virus (HBV) infection is a major public health problem. Recently, the human liver bile acid transporter Na(+)/taurocholate cotransporting polypeptide (NTCP) has been identified as an HBV specific receptor. NTCP expression is known to be strongly regulated by IL-6. This study was aimed at characterizing the effect of IL-6 on HBV entry. HBV entry was inhibited by up to 90% when cells were pretreated with IL-6 as shown by a strong inhibition of long term HBsAg secretion. This effect was confirmed by showing a severe reduction of intracellular HBV cccDNA. In parallel, we observed a 98% decrease in NTCP mRNA steady state level and an 80% reduction in NTCP-mediated taurocholate uptake. IL-6-mediated inhibition of NTCP-mediated taurocholate uptake and viral entry exhibited similar dose-dependence and kinetics while restoration of NTCP expression suppressed the inhibitory effect of IL-6. NTCP-mediated HBV entry is therefore markedly inhibited by IL-6.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (Inserm), U1085, Institut de Recherche Santé Environnement et Travail (IRSET), Rennes, France; Université de Rennes 1, F-35043 Rennes, France; Fédération de Recherche BioSit de Rennes UMS 3480, F-35043 Rennes, France.
authors.forename: Fidaa
authors.initials: F
authors.lastname: Bouezzedine
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (Inserm), U1085, Institut de Recherche Santé Environnement et Travail (IRSET), Rennes, France; Université de Rennes 1, F-35043 Rennes, France; Fédération de Recherche BioSit de Rennes UMS 3480, F-35043 Rennes, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Fardel
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (Inserm), U1085, Institut de Recherche Santé Environnement et Travail (IRSET), Rennes, France; Université de Rennes 1, F-35043 Rennes, France; Fédération de Recherche BioSit de Rennes UMS 3480, F-35043 Rennes, France. Electronic address: philippe.gripon@univ-rennes1.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Gripon
mesh_terms: D015536:Down-Regulation; D056945:Hep G2 Cells; D006509:Hepatitis B / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics / Q000502:physiology*; D022781:Hepatocytes / Q000378:metabolism / Q000821:virology; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics* / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D027981:Symporters / Q000235:genetics* / Q000378:metabolism; D053586:Virus Internalization
chemical_list: D015850:Interleukin-6; D029363:Organic Anion Transporters, Sodium-Dependent; D011991:Receptors, Virus; D027981:Symporters; C071908:sodium-bile acid cotransporter
keywords: Cytokines; HepaRG; Hepatitis B virus; Hepatocytes; IL-6; Inflammation; NTCP; Viral entry