Functional analysis of the cholesterol transporter Niemann-Pick C1 during Hepatitis E virus infection

• Applicant: Dr. Mara Klöhn
• Subject Area: Virology ; Gastroenterology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 556170877

The hepatitis E virus (HEV) is a long-neglected RNA virus and the major causative agent of acute viral hepatitis in humans worldwide. Current therapeutic options against HEV are limited and frequently accompanied with severe side effects. New approaches are urgently required to safely and effectively treat HEV infections. One potential target molecule is the membrane protein Niemann-Pick C1, which facilitates the transport of cholesterol and other lipids into the cell and is also exploited by various viruses to invade susceptible host cells. Using an HEV cell culture system, we recently observed that pharmacologic inhibition of NPC1 prevents HEV infection, suggesting an essential role of NPC1 during HEV virion transport. NPC1 could either serve as an endosomal receptor for HEV and interact with the viral capsid protein to enable genome transport into the cytoplasm. Alternatively, NPC1 may be required to maintain an endosomal environment with appropriate cholesterol levels for HEV to infect a cell. The proposed project “PickHEV” aims to elucidate the role of NPC1 during HEV infection and thereby provide new insights into the molecular mechanisms of HEV entry into host cells to open new avenues for the development of pharmacological strategies against HEV in the long term.

• DFG Programme: Research Grants