Molecular Mechanisms of the Hepatitis E Virus Life Cycle and Host Range

Abstract

At least 20 million hepatitis E virus (HEV) infections occur annually, with >3 million symptomatic cases and ~60,000 fatalities. Hepatitis E is generally self-limiting with a case fatality rate of 0.5-3% in young adults. However, it can cause up to 30% mortality in pregnant women in the third trimester, and can become chronic in immunocompromised individuals such as those receiving organ transplants or chemotherapy and individuals with HIV infection. HEV is transmitted primarily via the fecal–oral route, and was previously thought to be a public health concern only in developing countries. It is now also being frequently reported in industrialized countries, where it is transmitted zoonotically, or through organ transplantation or blood transfusions. Although a vaccine for HEV has been developed, it is only licensed in China. Additionally, no effective, non-teratogenic and specific treatments against HEV infections are currently available. Although progress has been made in characterizing HEV biology, the scarcity of adequate experimental platforms has hampered further research. The work presented in this dissertation advances our knowledge on HEV in three key areas: (i) the development of screening tools for and the identification of novel therapeutic compounds against HEV (Chapter 2); (ii) understanding the range of hosts susceptible to HEV infection (Chapter 3), and (iii) elucidating the mechanisms through which the virus replicates its genome and exits from the host cell (Chapters 4-5).