ArticleGastroenterology2018
Pan-Genotype Hepatitis E Virus Replication in Stem Cell-Derived Hepatocellular Systems.
Article in Gastroenterology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 67 citations in OpenAlex.
- The evolution of in vitro culture systems for the study of hepatitis E virus infection.Virology · 2026Review
- EIF4H and YBX1 are essential host factors for hepatitis E virus replication and pathogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- Virological and immunological determinants of hepatitis E virus infection outcomes.Current opinion in virology · 2025Review
- Application of Induced Pluripotent Stem Cells (iPSCs) in Hereditary and Viral Diseases of the Liver: Modeling and Treatment.International journal of molecular sciences · 2025Review
- The hepatitis E virus capsid protein ORF2 counteracts cell-intrinsic antiviral responses to enable persistent replication in cell culture.PLoS pathogens · 2025Article
- Single-cell analysis of mature hepatocytes reveals an IRF1-driven restriction of HDV infection.JHEP reports : innovation in hepatology · 2025Article
- Plasmacytoid dendritic cell sensing of hepatitis E virus is shaped by both viral and host factors.Life science alliance · 2025Article
- Research Progress on Hepatitis E Virus Culture.Pathogens (Basel, Switzerland) · 2025Review
- Broadly neutralizing antibodies isolated from HEV convalescents confer protective effects in human liver-chimeric mice.Nature communications · 2025Article
- Hepatitis E virus infects human testicular tissue and Sertoli cells.Emerging microbes & infections · 2024Article
- Hepatitis E virus: from innate sensing to adaptive immune responses.Nature reviews. Gastroenterology & hepatology · 2024Review
- An hepatitis B and D virus infection model using human pluripotent stem cell-derived hepatocytes.EMBO reports · 2024Article
- Hepatitis E Virus: What More Do We Need to Know?Medicina (Kaunas, Lithuania) · 2024Review
- Virus-Host Protein Interaction Network of the Hepatitis E Virus ORF2-4 by Mammalian Two-Hybrid Assays.Viruses · 2023Article
- The hepatitis E virus ORF1 hypervariable region confers partial cyclophilin dependency.The Journal of general virology · 2023Article
- Article
- Liver Organoid Potential Application for Hepatitis E Virus Infection.Advances in experimental medicine and biology · 2023Article
- Immunobiology and Host Response to HEV.Advances in experimental medicine and biology · 2023Article
- Puzzles for Hepatitis E Virus.Advances in experimental medicine and biology · 2023Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsThe 4 genotypes of hepatitis E virus (HEV) that infect humans (genotypes 1-4) vary in geographical distribution, transmission, and pathogenesis. Little is known about the properties of HEV or its hosts that contribute to these variations. Primary isolates grow poorly in cell culture; most studies have relied on variants adapted to cancer cell lines, which likely alter virus biology. We investigated the infection and replication of primary isolates of HEV in hepatocyte-like cells (HLCs) derived from human embryonic and induced pluripotent stem cells.
methodsUsing a cell culture-adapted genotype 3 strain and primary isolates of genotypes 1 to 4, we compared viral replication kinetics, sensitivity to drugs, and ability of HEV to activate the innate immune response. We studied HLCs using quantitative reverse-transcriptase polymerase chain reaction and immunofluorescence assay and enzyme-linked immunosorbent assays. We used an embryonic stem cell line that can be induced to express the CRISPR-Cas9 machinery to disrupt the peptidylprolyl isomerase A gene, encoding cyclophilin A (CYPA), a protein reported to inhibit replication of cell culture-adapted HEV. We further modified this line to rescue expression of CYPA before terminal differentiation to HLCs and performed HEV infection studies.
resultsHLCs were permissive for infection by nonadapted, primary isolates of HEV genotypes 1 to 4. HEV infection of HLCs induced a replication-dependent type III interferon response. Replication of primary HEV isolates, unlike the cell culture-adapted strain, was not affected by disruption of the peptidylprolyl isomerase A gene or exposure to the CYPA inhibitor cyclosporine A.
conclusionsCell culture adaptations alter the replicative capacities of HEV. HLCs offer an improved, physiologically relevant, and genetically tractable system for studying the replication of primary HEV isolates. HLCs could provide a model to aid development of HEV drugs and a system to guide personalized regimens, especially for patients with chronic hepatitis E who have developed resistance to ribavirin.
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