Primary biliary acids inhibit hepatitis D virus (HDV) entry into human hepatoma cells expressing the sodium-taurocholate cotransporting polypeptide (NTCP)
- Background: The sodium-taurocholate cotransporting polypeptide (NTCP) is both a key bile acid (BA) transporter mediating uptake of BA into hepatocytes and an essential receptor for hepatitis B virus (HBV) and hepatitis D virus (HDV). In this study we aimed to characterize to what extent and through what mechanism BA affect HDV cell entry. Methods: HuH-7 cells stably expressing NTCP (HuH-7/NTCP) and primary human hepatocytes (PHH) were infected with in vitro generated HDV particles. Infectivity in the absence or presence of compounds was assessed using immunofluorescence staining for HDV antigen, standard 50% tissue culture infectious dose (TCID50) assays and quantitative PCR. Results: Addition of primary conjugated and unconjugated BA resulted in a dose dependent reduction in the number of infected cells while secondary, tertiary and synthetic BA had a lesser effect. This effect was observed both in HuH-7/NTCP and in PHH. Other replication cycle steps such as replication and particle assembly and release were unaffected. Moreover, inhibitory BA competed with a fragment from the large HBV envelope protein for binding to NTCP-expressing cells. Conversely, the sodium/BA-cotransporter function of NTCP seemed not to be required for HDV infection since infection was similar in the presence or absence of a sodium gradient across the plasma membrane. When chenodeoxycolic acid (15 mg per kg body weight) was administered to three chronically HDV infected individuals over a period of up to 16 days there was no change in serum HDV RNA. Conclusions: Primary BA inhibit NTCP-mediated HDV entry into hepatocytes suggesting that modulation of the BA pool may affect HDV infection of hepatocytes.
Author: | Isabel Veloso Alves Pereira, Bettina Buchmann, Lisa Sandmann, Kathrin Sprinzl, Verena Schlaphoff, Katinka DöhnerORCiDGND, Florian VondranORCiDGND, Christoph SarrazinGND, Michael P. MannsORCiDGND, Cláudia Pinto Marques Souza de Oliveira, Beate SodeikORCiDGND, Sandra CiesekORCiDGND, Thomas von HahnORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-370406 |
DOI: | https://doi.org/10.1371/journal.pone.0117152 |
ISSN: | 1932-6203 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/25646622 |
Parent Title (English): | PLoS One |
Publisher: | PLoS |
Place of publication: | Lawrence, Kan. |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2015/02/03 |
Date of first Publication: | 2015/02/03 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2015/02/16 |
Volume: | 10 |
Issue: | (2): e0117152 |
Page Number: | 16 |
Note: | Copyright: © 2015 Veloso Alves Pereira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited |
HeBIS-PPN: | 36837548X |
Institutes: | Medizin / Medizin |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - Namensnennung 4.0 |