Session topic


Title: Targeting cholesterol metabolism as efficient antiviral strategy against the Hepatitis E virus
ID: O 63
Type: Abstract talk
Talk time: 12 + 3 min
Session: Workshop 11
Antivirals and resistance II

Speaker: Mirco Glitscher (Langen/DE)

Abstract - Text

Abstract text (incl. references and figure legends)


The Hepatitis E virus is a major causes of an acute, viral hepatitis. Although posing a risk for the health of many people, a majority of the virus" life cycle remains elusive. This results in treatments being very limited, making novel antivirals urgently needed. A central aspect of the viral life cycle displays release via endosomal system, which is highly dependent on cholesterol.


The aim of this study was to investigate the dependency of viral release on cholesterol and to correlate changes in cholesterol homeostasis with impacts on the viral life cycle. Using this knowledge, a further aim was to design a novel strategy for an antiviral treatment against HEV.


Intracellular cholesterol-content and changes in gene-expression of cholesterol-related genes were assessed via microscopy and transcriptome-analysis, respectively. Blood-lipids and HEV-RNA were routinely quantified in chronically infected patients during follow-up visits. Cholesterol-levels of cells were modulated via exogenous sources or drugs and subsequent impacts on HEV were monitored using qPCR, Western Blot, microscopy, virus-titration and density-gradient centrifugation.


In HEV-infected cells, decreased levels of cholesterol were found. Similarly, HEV-infection decreased serum-lipid concentrations of chronically infected patients. Importantly, statin-treatment herein increased viral titers in vivo and caused similar effects in vitro by inducing viral release. On the contrary, elevating intracellular cholesterol via LDL or 25-hydroxycholesterol strongly reduced viral release, which was found to be due to enhanced lysosomal degradation of HEV. This knowledge was applied for investigating cholesterol-modulating drugs for their antiviral capacity against HEV in vitro. Especially the p-glycoprotein inhibitor PSC833 (Valspodar) and the PPARα-agonist Fenofibrate increased intracellular cholesterol drastically. Induced by this, HEV was found to be degraded lysosomally in a cholesterol-dependent manner, which resulted in significantly reduced viral release.


This study highlights the importance of an intact cholesterol-homeostasis for HEV-release and thereby identifies a potent target for antiviral strategies. Especially Fenofibrate is considered a promising novel treatment against the virus. Beyond this, the study may help clinicians to better evaluate co-treatments in HEV-infected patients, since statins seem to be counter indicated.