Lipase inhibitor orlistat prevents hepatitis B virus infection by targeting an early step in the virus life cycle.
Antiviral Res. 151, 4-7 (2018)
Hepatitis B Virus (HBV) is a strictly hepatotropic pathogen which is very efficiently targeted to the liver and into its host cell, the hepatocyte. The sodium taurocholate co-transporting polypeptide (NTCP) has been identified as a key virus entry receptor, but the early steps in the virus life cycle are still only barely understood. Here, we investigated the effect of lipase inhibition and lipoprotein uptake on HBV infection using differentiated HepaRG cells and primary human hepatocytes. We found that an excess of triglyceride rich lipoprotein particles in vitro diminished HBV infection and a reduced hepatic virus uptake in vivo if apolipoprotein E is lacking indicating virus transport along with lipoproteins to target hepatocytes. Moreover, we showed that HBV infection of hepatocytes was inhibited by the broadly active lipase inhibitor orlistat, approved as a therapeutic agent which blocks neutral lipid hydrolysis activity. Orlistat treatment targets HBV infection at a post-entry step and inhibited HBV infection during virus inoculation strongly in a dose-dependent manner. In contrast, orlistat had no effect on HBV gene expression or replication or when added after HBV infection. Taken together, our data indicate that HBV connects to the hepatotropic lipoprotein metabolism and that inhibition of cellular hepatic lipase(s) may allow to target early steps of HBV infection.
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Publication type
Article: Journal article
Document type
Scientific Article
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Keywords
Binding; Proteoglycans; Albumin; Liver; Site; Rats
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Language
english
Publication Year
2018
Prepublished in Year
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2018
ISSN (print) / ISBN
0166-3542
e-ISSN
1872-9096
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Volume: 151,
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Pages: 4-7
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Elsevier
Publishing Place
Amsterdam
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Peer reviewed
POF-Topic(s)
30203 - Molecular Targets and Therapies
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s)
Immune Response and Infection
PSP Element(s)
G-502700-003
G-508600-010
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Erfassungsdatum
2018-01-10