ArticlePLoS pathogens2018
Palmitoylation mediates membrane association of hepatitis E virus ORF3 protein and is required for infectious particle secretion.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Hepatitis E Virus (HEV) Infection in the Context of the One Health Approach: A Systematic Review.Pathogens (Basel, Switzerland) · 2025Pooled it
- Transferrin receptor 1 is required for efficient hepatitis E virus production.PLoS pathogens · 2026Article
- Anatid herpesvirus 1 UL51 protein is palmitoylated by DHHC9 and DHHC18 for viral replication and virulence.PLoS pathogens · 2026Article
- Hepatitis E ORF2 Blocks Trophoblast Autophagy to Induce Miscarriage via LC3B Binding Rather than PI3K/Akt/mTOR Pathway Suppression.Microorganisms · 2026Article
- S-palmitoylation and depalmitoylation at the interface of animal virus-host interactions.Frontiers in cellular and infection microbiology · 2026Review
- 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
- Protein palmitoylation in hepatic diseases: Functional insights and therapeutic strategies.Journal of advanced research · 2025Review
- The leader of the capsid protein fromJournal of virology · 2025Article
- Monitoring of hepatitis E virus infection and replication by functional tagging of the ORF2 protein.JHEP reports : innovation in hepatology · 2025Article
- The CP123L protein of African swine fever virus is a membrane-associated, palmitoylated protein required for viral replication.Journal of virology · 2025Article
- Palmitoylation-dependent association with Annexin II directs hepatitis E virus ORF3 sorting into vesicles and quasi-enveloped virions.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A comprehensive review on seroepidemiology and molecular epidemiology of hepatitis E Virus in Iran.Gastroenterology and hepatology from bed to bench · 2025Review
- 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
- Hepatitis E virus: from innate sensing to adaptive immune responses.Nature reviews. Gastroenterology & hepatology · 2024Review
- Viral Hepatitis: Host Immune Interaction, Pathogenesis and New Therapeutic Strategies.Pathogens (Basel, Switzerland) · 2024Review
- 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
- Multiple Functions of Hepatitis E Virus ORF3.Microorganisms · 2024Review
- Hepatitis E Virus: What More Do We Need to Know?Medicina (Kaunas, Lithuania) · 2024Review
- Characterization of virus‒host recombinant variants of the hepatitis E virus.Journal of virology · 2024Article
- Hepatitis E virus ORF3 protein hijacking thioredoxin domain-containing protein 5 (TXNDC5) for its stability to promote viral particle release.Journal of virology · 2024Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatitis E virus (HEV) is a positive-strand RNA virus encoding 3 open reading frames (ORF). HEV ORF3 protein is a small, hitherto poorly characterized protein involved in viral particle secretion and possibly other functions. Here, we show that HEV ORF3 protein forms membrane-associated oligomers. Immunoblot analyses of ORF3 protein expressed in cell-free vs. cellular systems suggested a posttranslational modification. Further analyses revealed that HEV ORF3 protein is palmitoylated at cysteine residues in its N-terminal region, as corroborated by 3H-palmitate labeling, the investigation of cysteine-to-alanine substitution mutants and treatment with the palmitoylation inhibitor 2-bromopalmitate (2-BP). Abrogation of palmitoylation by site-directed mutagenesis or 2-BP treatment altered the subcellular localization of ORF3 protein, reduced the stability of the protein and strongly impaired the secretion of infectious particles. Moreover, selective membrane permeabilization coupled with immunofluorescence microscopy revealed that HEV ORF3 protein is entirely exposed to the cytosolic side of the membrane, allowing to propose a model for its membrane topology and interactions required in the viral life cycle. In conclusion, palmitoylation determines the subcellular localization, membrane topology and function of HEV ORF3 protein in the HEV life cycle.
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Registered trials
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