Understanding of enhanced hepatitis E virus infection in polarised hepatocytes

Hepatitis E virus (HEV) causes ~20 million infections annually, yet lacks specific therapies or universally approved vaccines. Current in vitro models fail to replicate hepatocyte polarity, crucial for HEV propagation. We propose using novel polarized hepatoma cell models (PLC-PRF-5 and Huh-7.5) that support high-efficiency infection with clinical HEV genotype 3 isolates. Leveraging cryo-soft X-ray tomography at BL09 MISTRAL, we will create a 3D ultrastructural atlas of HEV-infected cells, focusing on cell polarity effects and tight junction reorganization. This approach builds on SXT's success in studying other viruses, offering unprecedented insights into HEV infection dynamics. Results will directly inform understanding of HEV infection mechanisms and guide the development of targeted therapeutic strategies, addressing a critical global health challenge.

The proposal comes from the consortium of three laboratories - M. Harkiolaki, Warwick University, UK; Venera Weinhardt, Heidelberg University, Germany; and Nicola Fletcher, University College Dublin (at the time of the proposal, not registered as a user due to conflict with summer holidays).