| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 6139010 | Virology | 2015 | 9 Pages |
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.
Keywords
PBSIFN γmethylthiazoletetrazoliumhepatocyte nuclear factor 1 alphasodium taurocholate co-transporting polypeptideHepaRGHNF4αPHHNtcpcccDNAHNF1αHBsAgIL-1βALTRT-qPCRJnkTNFαOSMIL-6c-Jun N-terminal kinasesDMSOcovalently closed circular DNAprimary human hepatocyteHepatocytesMTTAlanine aminotransferaseHepatitis B surface antigeninflammationoncostatin Minterleukin 1 betainterleukin 6tumor necrosis factor alphaDimethyl sulfoxideCytokineshepatocyte nuclear factor 4 alphaPhosphate buffered salineHBVreal-time quantitative polymerase chain reactionViral entryhepatitis B viruspolyethylene glycolPEGInterferon gamma
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Authors
Fidaa Bouezzedine, Olivier Fardel, Philippe Gripon,