Hepatitis E virus (HEV) is a leading cause of acute viral hepatitis, with an estimated 20 million infections annually. HEV genotype 1 (HEV-1) infection, in particular, has been associated with severe disease progression and fulminant hepatitis in pregnant women. Currently, treatment options are limited, and despite notable research progress in recent years, key aspects of the molecular mechanisms and host–virus interactions remain unresolved.

A limiting factor for HEV-1 research has been the lack of an efficient in vitro cell culture system. Here, we established a recently described HEV-1 cell culture model using colorectal adenocarcinoma-derived Caco-2 cells. We were able to produce infectious viral particles, observe and validate infections in Caco-2 cells using immunofluorescence microscopy, and investigate replication efficiencies using a subgenomic HEV-1 replicon. Based on this cell culture model, we deepened our studies, focusing on the initial steps of the viral life cycle. Within the research of NPC1 as a host factor for HEV-3 infection (see the abstract by Emely Richter), we were able to confirm the effectiveness of the NPC1 inhibitor itraconazole during HEV-1 infection, postulating the role of NPC1 as a host factor for HEV-1. Additionally, we verified the effect of the pan-cathepsin inhibitor K11777, confirming the role of cathepsins in HEV-1 entry.

Furthermore, we investigated the effect of different interferon-alpha subtypes on HEV-1 replication. In the future, we want to deepen our research by looking into the mechanisms and pathways modulated during HEV-1 infection by integrating RNA-sequencing of HEV‑1 infected cells.

Overall, this project aims to elucidate the underlying viral and host mechanisms of HEV-1 infection and its pathogenesis.