Hepatitis E Research
We use stem cell-derived culture models to study hepatitis E virus (HEV) life cycle and HEV-host interactions.
The Dao Thi lab uses stem cell-derived culture models to study hepatitis E virus (HEV). With about 20 million infections each year, leading to more than 3 million symptomatic cases and ~60000 fatalities, HEV is believed to be the most common cause of acute hepatitis in the world. Despite increasing awareness, HEV remains an understudied virus. A contributor to the poor understanding is the difficulty to propagate HEV in cell culture. To overcome these limitations, we use embryonic or induced pluripotent stem cell (hESC/iPSC)-derived cell culture models, in particular stem-cell derived hepatocyte-like cells (HLCs). Unlike conventionally used hepatoma cells, we found that HLCs are permissive for infection by primary isolates of all four HEV genotypes that can infect humans. HLCs therefore enable studies of authentic pan-genotype HEV biology. Further, the capability to study replication of non-adapted HEV isolates in tandem with autologous, patient-derived iPSCs enables personalized models of HEV infection and will serve as a platform for testing novel anti-HEV treatments (Figure 1).
Dao Thi VL, Wu X, Belote RL, Andreo U, Takacs CN, Fernandez JP, Vale-Silva LA, Decker CC, Fu RM, Qu B, Uryu K, Molina H, Saeed M, Steinmann E, Urban S, Singarja RR, Schneider WM, Simon SM, and Rice CM (2020). Stem cell-derived polarized hepatocytes. Nature Commun. 11(1):1677.
Dao Thi VL, Herbst K, Boerner K, Meurer M, Kremer PML, Kirrmaier D, Freistaedter A, Papagiannidis D, Galmozzi C, Stanifer ML, Boulant S, Klein S, Chlanda P, Khalid D, Barreto Mirranda I, Schnitzler P, Kräusslich HG, Knop M, and Anders S (2020). A colorimetric RT-LAMP assay and LAMP-sequencing for detecting SARS-CoV-2 RNA in clinical samples. Sci Transl Med. 12(556):eabc7075.
Herbst K, Meurer M, Kirrmaier D, Anders S, Knop M, Dao Thi VL (2021). Colorimetric RT-LAMP and LAMP-sequencing for Detecting SARS-CoV-2 RNA in Clinical Samples. Bio Protoc. 11(6):e3964.