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Antiviral Res. 2018 Mar;151:4-7. doi: 10.1016/j.antiviral.2018.01.001. Epub 2018 Jan 5.

Lipase inhibitor orlistat prevents hepatitis B virus infection by targeting an early step in the virus life cycle.

Author information

1
Institute of Virology, Technische Universität München/Helmholtz Zentrum München, Trogerstrasse 30, 81675 Munich, Germany.
2
Institute of Virology, Technische Universität München/Helmholtz Zentrum München, Trogerstrasse 30, 81675 Munich, Germany; German Center for Infection Research (DZIF), Munich site, Germany.
3
Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar der Technischen Universität München, Germany.
4
Institute of Experimental Biomedicine, University Hospital Würzburg, Josef-Schneider-Str. 2, Würzburg, 97080, Germany.
5
Institute of Virology, Technische Universität München/Helmholtz Zentrum München, Trogerstrasse 30, 81675 Munich, Germany; German Center for Infection Research (DZIF), Munich site, Germany. Electronic address: protzer@tum.de.

Abstract

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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