Interleukin 6 inhibits HBV entry through NTCP down regulation

被引：84
作者：
Bouezzedine, Fidaa [1 ,2 ,3 ]
Fardel, Olivier [1 ,2 ,3 ]
Gripon, Philippe [1 ,2 ,3 ]
机构：
[1] INSERM, IRSET, U1085, F-35043 Rennes, France
[2] Univ Rennes 1, F-35043 Rennes, France
[3] Federat Rech BioSit Rennes, UMS 3480, F-35043 Rennes, France
来源：
VIROLOGY | 2015年 / 481卷
关键词：
Cytokines; IL-6; Inflammation; Hepatitis B virus; Hepatocytes; HepaRG; NTCP; Viral entry; HEPATITIS-B-VIRUS; ADULT HUMAN HEPATOCYTES; LARGE SURFACE PROTEIN; LIVER-REGENERATION; TRANSPORTER EXPRESSION; FUNCTIONAL EXPRESSION; DRUG TRANSPORTERS; CELL-LINE; INFECTION; RESPONSES;
D O I：
10.1016/j.virol.2015.02.026
中图分类号：
Q93 [微生物学];
学科分类号：
071005 ; 100705 ;
摘要：
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. (C) 2015 Elsevier Inc. All rights reserved.
引用
收藏
页码：34 / 42
页数：9
相关论文
共 42 条
[1]   RAPID ACTIVATION OF THE STAT3 TRANSCRIPTION COMPLEX IN LIVER-REGENERATION [J].
CRESSMAN, DE ;
DIAMOND, RH ;
TAUB, R .
HEPATOLOGY, 1995, 21 (05) :1443-1449
[2]   Early kinetics of innate and adaptive immune responses during hepatitis B virus infection [J].
Fisicaro, P. ;
Valdatta, C. ;
Boni, C. ;
Massari, M. ;
Mori, C. ;
Zerbini, A. ;
Orlandini, A. ;
Sacchelli, L. ;
Missale, G. ;
Ferrari, C. .
GUT, 2009, 58 (07) :974-982
[3]   Principles of hepatic organic anion transporter regulation during cholestasis, inflammation and liver regeneration [J].
Geier, Andreas ;
Wagner, Martin ;
Dietrich, Christoph G. ;
Trauner, Michael .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2007, 1773 (03) :283-308
[4]   REPRODUCIBLE HIGH-LEVEL INFECTION OF CULTURED ADULT HUMAN HEPATOCYTES BY HEPATITIS-B VIRUS - EFFECT OF POLYETHYLENE-GLYCOL ON ADSORPTION AND PENETRATION [J].
GRIPON, P ;
DIOT, C ;
GUGUENGUILLOUZO, C .
VIROLOGY, 1993, 192 (02) :534-540
[5]   Efficient inhibition of hepatitis B virus infection by acylated peptides derived from the large viral surface protein [J].
Gripon, P ;
Cannie, I ;
Urban, S .
JOURNAL OF VIROLOGY, 2005, 79 (03) :1613-1622
[6]   Infection of a human hepatoma cell line by hepatitis B virus [J].
Gripon, P ;
Rumin, S ;
Urban, S ;
Le Seyec, J ;
Glaise, D ;
Cannie, I ;
Guyomard, C ;
Lucas, J ;
Trepo, C ;
Guguen-Guillouzo, C .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (24) :15655-15660
[7]   HEPATITIS-B VIRUS-INFECTION OF ADULT HUMAN HEPATOCYTES CULTURED IN THE PRESENCE OF DIMETHYL-SULFOXIDE [J].
GRIPON, P ;
DIOT, C ;
THEZE, N ;
FOUREL, I ;
LOREAL, O ;
BRECHOT, C ;
GUGUENGUILLOUZO, C .
JOURNAL OF VIROLOGY, 1988, 62 (11) :4136-4143
[8]   MYRISTYLATION OF THE HEPATITIS-B VIRUS LARGE SURFACE PROTEIN IS ESSENTIAL FOR VIRAL INFECTIVITY [J].
GRIPON, P ;
LESEYEC, J ;
RUMIN, S ;
GUGUENGUILLOUZO, C .
VIROLOGY, 1995, 213 (02) :292-299
[9]   Not Interferon, but Interleukin-6 Controls Early Gene Expression in Hepatitis B Virus Infection [J].
Hoesel, Marianna ;
Quasdorff, Maria ;
Wiegmann, Katja ;
Webb, Dennis ;
Zedler, Uta ;
Broxtermann, Mathias ;
Tedjokusumo, Raindy ;
Esser, Knud ;
Arzberger, Silke ;
Kirschning, Carsten J. ;
Langenkamp, Anja ;
Falk, Christine ;
Buening, Hildegard ;
Rose-John, Stefan ;
Protzer, Ulrike .
HEPATOLOGY, 2009, 50 (06) :1773-1782
[10]   Role of liver-enriched transcription factors and nuclear receptors in regulating the human, mouse, and rat NTCP gene [J].
Jung, D ;
Hagenbuch, B ;
Fried, M ;
Meier, PJ ;
Kullak-Ublick, GA .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2004, 286 (05) :G752-G761
12345