About 20 million people are infected with the hepatitis E virus (HEV) every year. Most infections spontaneously disappear with limited symptoms, but a small proportion of infected people experience symptoms similar to those caused by hepatitis A infection (muscle and joint pain, fatigue, vomiting, jaundice and modest liver damage). However, people who suppress the immune system due to chemotherapy, organ transplantation, HIV or pregnancy, experience severe acute liver disease, acute liver failure and even death. HEV is primarily transmitted via the faecal-oral route and until recently was considered a problem of developing countries, where poor hygiene and sanitation facilities promote viral spread. However, recent epidemiological data show that HEV is also circulating in industrialized countries. This is because HEV not only infects people, but also various other species such as pigs, deer and shellfish. The consumption of raw or insufficiently heated contaminated food can result in HEV infection. This project aims at a better understanding of the morphological, molecular and functional changes that occur in the human liver during HEV infection. We are in a unique position to conduct these studies because we have developed human liver chimeric mice. Since these animals are deficient in the adaptive immune system, we expect that the infection will evolve in a similar way as in patients with immunosuppression. Finally, we intend to use our model for the evaluation of new antiviral therapies.