期刊
VIROLOGY
卷 481, 期 -, 页码 34-42出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2015.02.026
关键词
Cytokines; IL-6; Inflammation; Hepatitis B virus; Hepatocytes; HepaRG; NTCP; Viral entry
类别
资金
- ANRS (Agence nationale de recherche contre le sida et les hepatites virales)
- Region Bretagne
- Ligue Nationale contre le Cancer
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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