ArticleFrontiers in microbiology2022
Processing and Subcellular Localization of the Hepatitis E Virus Replicase: Identification of Candidate Viral Factories.
Article in Frontiers in microbiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 36 citations in OpenAlex.
- 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
- Hepatitis E Virus ORF1 Polyprotein Harbors a Pocket-Like Cavity That Is Vital for Virus Replication and Represents a Novel Antiviral Target.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The hepatitis E virus capsid protein ORF2 counteracts cell-intrinsic antiviral responses to enable persistent replication in cell culture.PLoS pathogens · 2025Article
- Proteasomal processing of the viral replicase ORF1 facilitates HEV-induced liver fibrosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Cell line-dependent release of quasi-enveloped hepatitis E virus reveals alternative Golgi-associated egress in the absence of pORF3.Frontiers in cellular and infection microbiology · 2025Article
- Role of Rab13, Protein Kinase A, and Zonula Occludens-1 in Hepatitis E Virus Entry and Cell-to-Cell Spread: Comparative Analysis of Quasi-Enveloped and Non-Enveloped Forms.Pathogens (Basel, Switzerland) · 2024Article
- The AP-1 adaptor complex is essential for intracellular trafficking of the ORF2 capsid protein and assembly of Hepatitis E virus.Cellular and molecular life sciences : CMLS · 2024Article
- Oxysterol binding protein (OSBP) contributes to hepatitis E virus replication.Virology journal · 2024Article
- A genome-wide CRISPR/Cas9 screen identifies a role for Rab5A and early endosomes in hepatitis E virus replication.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Development of a HiBiT-tagged reporter hepatitis E virus and its utility as an antiviral drug screening platform.Journal of virology · 2023Article
- Three Distinct Reporter Systems of Hepatitis E Virus and Their Utility as Drug Screening Platforms.Viruses · 2023Review
- Thrombin cleavage of the hepatitis E virus polyprotein at multiple conserved locations is required for genome replication.PLoS pathogens · 2023Article
- Hepatitis E Virus Protease Inhibits the Activity of Eukaryotic Initiation Factor 2-Alpha Kinase 4 and Promotes Virus Survival.Journal of virology · 2023Article
- The PRMT5/WDR77 complex restricts hepatitis E virus replication.PLoS pathogens · 2023Article
- Expanding the Hepatitis E Virus Toolbox: Selectable Replicons and Recombinant Reporter Genomes.Viruses · 2023Review
- Article
- A ribavirin-induced ORF2 single-nucleotide variant produces defective hepatitis E virus particles with immune decoy function.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatitis E virus (HEV) is the major cause of acute hepatitis worldwide. HEV is a positive-sense RNA virus expressing three open reading frames (ORFs). ORF1 encodes the ORF1 non-structural polyprotein, the viral replicase which transcribes the full-length genome and a subgenomic RNA that encodes the structural ORF2 and ORF3 proteins. The present study is focused on the replication step with the aim to determine whether the ORF1 polyprotein is processed during the HEV lifecycle and to identify where the replication takes place inside the host cell. As no commercial antibody recognizes ORF1 in HEV-replicating cells, we aimed at inserting epitope tags within the ORF1 protein without impacting the virus replication efficacy. Two insertion sites located in the hypervariable region were thus selected to tolerate the V5 epitope while preserving HEV replication efficacy. Once integrated into the infectious full-length Kernow C-1 p6 strain, the V5 epitopes did neither impact the replication of genomic nor the production of subgenomic RNA. Also, the V5-tagged viral particles remained as infectious as the wildtype particles to Huh-7.5 cells. Next, the expression pattern of the V5-tagged ORF1 was compared in heterologous expression and replicative HEV systems. A high molecular weight protein (180 kDa) that was expressed in all three systems and that likely corresponds to the unprocessed form of ORF1 was detected up to 25 days after electroporation in the p6 cell culture system. Additionally, less abundant products of lower molecular weights were detected in both in cytoplasmic and nuclear compartments. Concurrently, the V5-tagged ORF1 was localized by confocal microscopy inside the cell nucleus but also as compact perinuclear substructures in which ORF2 and ORF3 proteins were detected. Importantly, using
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