Recapitulating hepatitis E virus-host interactions and facilitating antiviral drug discovery in human liver-derived organoids.

ABSTRACT: Hepatotropic viruses naturally have narrow host and tissue tropisms, challenging the development of robust experimental models. The advent of organoid technology provides a unique opportunity for moving the field forward. Here, we demonstrate that three-dimensional cultured organoids from fetal and adult human liver with cholangiocyte or hepatocyte phenotype support hepatitis E virus (HEV) replication. Inoculation with infectious HEV particles demonstrates that human liver–derived organoids support the full life cycle of HEV infection. By directing organoids toward polarized monolayers in a transwell system, we observed predominantly apical secretion of HEV particles. Genome-wide transcriptomic and tRNAome analyses revealed robust host responses triggered by viral replication. Drug screeni

SUBMITTER: Li P 

PROVIDER: S-EPMC8769558 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature