Identification of host factors involved in hepatitis E virus RNA replication
Final Report Abstract
Over the past decade, it has become apparent that hepatitis E virus (HEV) is a pathogen of global significance. The heterogenous nature of HEV infections poses clinical challenges. Tropical HEV infections may lead to acute liver failure, especially in pregnant women, while autochthonous HEV infections may lead to acute-on-chronic liver failure in patients with underlying liver diseases. Despite increasing awareness, HEV remains an understudied virus with off-label RBV and pegylated interferon-α as the only available sub-optimal therapies. Treatment with these drugs can cause serious side effects and cannot be used for all patients or in resource-poor settings. Furthermore, mutations leading to RBV resistance have already been identified in chronic HEV patients. Thus, safer and more effective treatment options are needed. Historically, HEV has been difficult to propagate in cell culture, therefore limiting much of our understanding of HEV biology. Our work developing a range of novel state-of-the-art molecular tools, from HEV replicon systems to stem cellderived hepatocellular systems, will now allow us to characterize crucial virus life cycle steps such as RNA genome replication. The identification of viral and host determinants orchestrating the HEV life cycle is essential for the rational development of specific anti-HEV treatments.
Publications
- (2019) Embryonic or Induced Pluripotent Stem Cell-Derived Hepatocellular Systems for HCV Culture. Methods in molecular biology (Clifton, N.J.) 1911 121–135
Wu, Xianfang; Dao Thi, Viet Loan
(See online at https://doi.org/10.1007/978-1-4939-8976-8_8) - Sofosbuvir Inhibits Hepatitis E Virus Replication In Vitro and Results in an Additive Effect When Combined With Ribavirin. (2016) Gastroenterology 150, 82-85
Dao Thi VL, Debing Y, Wu X, Rice CM, Neyts J, Moradpour D, Gouttenoire J
(See online at https://doi.org/10.1053/j.gastro.2015.09.011)
