Robust hepatitis E virus infection and transcriptional response in human hepatocytes

In this study, we established a protocol based on the HEV genotype 3 p6 (Kernow C-1) and the human hepatoma cell lines HepG2 and HepG2/C3A with different media conditions to produce HEV cell culture-derived particles (HEVcc) with viral titers between 10e5 to 10e6 FFU/mL. Viral titers could be further enhanced by an HEV variant harboring a mutation in the RNA-dependent RNA polymerase. These HEVcc particles were infectious in primary human hepatocytes. RNA sequencing studies of HEV infected primary human hepatocytes demonstrated a temporally structured transcriptional defense response. In conclusion, this robust cell culture model of HEV infection provides a powerful tool for studying viral-host interactions that should facilitate the discovery of antiviral drugs and vaccines for this important zoonotic pathogen. Primary human hepatocytes (PHH) were inoculated with cell culture-derived HEV particles and changes in transcriptional profiles were assessed using RNAseq.