ArticleProceedings of the National Academy of Sciences of the United States of America2017
Hepatitis E virus ORF3 is a functional ion channel required for release of infectious particles.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 151 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
151 citing papers in PubMed, 218 citations in OpenAlex.
- Hepatitis E Virus Infection in Pregnant Women.Microorganisms · 2026Review
- Extra-Hepatic Manifestations of Hepatitis E Virus (HEV): A Narrative Review on Meningoencephalitis.Life (Basel, Switzerland) · 2026Review
- Transferrin receptor 1 is required for efficient hepatitis E virus production.PLoS pathogens · 2026Article
- Fatty acid regulation and phosphatidylethanolamine biosynthesis are important for hepatitis E virus replication.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Elbasvir Inhibits Hepatitis E Virus Internalization and, in Combination with Ribavirin, Achieves Sustained Viral Suppression In Vitro.Pathogens (Basel, Switzerland) · 2026Article
- The evolution of in vitro culture systems for the study of hepatitis E virus infection.Virology · 2026Review
- Integrated Bioinformatics Analysis Reveals the Impact of SHEV ORF3-Related LncRNA Network on Bile Secretion Pathway (ko 04976) in HepG2 Cells.Veterinary sciences · 2026Article
- 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
- GRP75 blocks hepatitis E virus infection by targeting HEV-ORF2 for degradation through chaperone-mediated autophagy and promoting IRF3 activation.Journal of virology · 2026Article
- Reactive oxygen species promotion drives auranofin's antiviral activity against hepatitis E virus.Journal of virology · 2026Article
- Hepatitis E ORF2 Blocks Trophoblast Autophagy to Induce Miscarriage via LC3B Binding Rather than PI3K/Akt/mTOR Pathway Suppression.Microorganisms · 2026Article
- The prion-like characteristic of ORF3 contributes to virion release and pathogenesis of hepatitis E virus.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Multiple Transcriptome Analyses Reveal the Selected lncRNA-mRNA and circRNA-mRNA Networks in HepG2 Cells Expressing Genotype 4 Swine Hepatitis E Virus ORF3.Veterinary sciences · 2025Article
- Virological and immunological determinants of hepatitis E virus infection outcomes.Current opinion in virology · 2025Review
- 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
- Comprehensive Bioinformatics Analysis the circRNAs of Viral Infection Associated Pathway in HepG2 Expressing ORF3 of Genotype IV Swine Hepatitis E Virus.Microorganisms · 2025Article
- Identification of Riboflavin Metabolism Pathway in HepG2 Cells Expressing Genotype IV Swine Hepatitis E Virus ORF3 Protein.Veterinary sciences · 2025Article
- Antiviral resistance and barrier integrity at the maternal-fetal interface restrict hepatitis E virus from crossing the placental barrier.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- First Insight into the Seroprevalence of Hepatitis E Virus and Associated Risk Factors Among Liver Transplant Recipients from Bulgaria.Vector borne and zoonotic diseases (Larchmont, N.Y.) · 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
91 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatitis E virus (HEV) is the leading cause of enterically transmitted viral hepatitis globally. Of HEV's three ORFs, the function of ORF3 has remained elusive. Here, we demonstrate that via homophilic interactions ORF3 forms multimeric complexes associated with intracellular endoplasmic reticulum (ER)-derived membranes. HEV ORF3 shares several structural features with class I viroporins, and the function of HEV ORF3 can be maintained by replacing it with the well-characterized viroporin influenza A virus (IAV) matrix-2 protein. ORF3's ion channel function is further evidenced by its ability to mediate ionic currents when expressed in Xenopus laevis oocytes. Furthermore, we identified several positions in ORF3 critical for its formation of multimeric complexes, ion channel activity, and, ultimately, release of infectious particles. Collectively, our data demonstrate a previously undescribed function of HEV ORF3 as a viroporin, which may serve as an attractive target in developing direct-acting antivirals.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.