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.
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页码：34 / 42
页数：9
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