ArticlePLoS pathogens2016
Endoplasmic Reticulum Stress Induced Synthesis of a Novel Viral Factor Mediates Efficient Replication of Genotype-1 Hepatitis E Virus.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers, 3 of them syntheses that pooled it.
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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.
The trial behind it
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
145 citing papers in PubMed, 3 syntheses or guidelines pooled it, 242 citations in OpenAlex.
- Pooled it
- Hepatitis E Virus (HEV) Infection in the Context of the One Health Approach: A Systematic Review.Pathogens (Basel, Switzerland) · 2025Pooled it
- Meta-Analysis of Human IgG anti-HEV Seroprevalence in Industrialized Countries and a Review of Literature.Viruses · 2019Pooled it
- Identification of Host Interaction Partners of the Hepatitis E Virus Internal Ribosome Entry Site-Like RNA Using RNA-Protein Interaction Detection Assay and Yeast Three-Hybrid Assay.Methods in molecular biology (Clifton, N.J.) · 2027Article
- 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
- 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
- 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
- GRP75 blocks hepatitis E virus infection by targeting HEV-ORF2 for degradation through chaperone-mediated autophagy and promoting IRF3 activation.Journal of virology · 2026Article
- Antiviral potential of zinc ion: mechanisms and applications in viral infections.Frontiers in 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
- Viral helicase and methyltransferase promote genotype one-hepatitis e virus internal ribosome entry site-like element activity.Npj viruses · 2025Article
- Differential miRNA signatures in Hepatitis E Virus Infection: Insights into acute, chronic, and pregnancy-related outcomes.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2025Review
- Network controllability analysis reveals the antiviral potential of Etravirine against hepatitis E virus infection.mSystems · 2025Article
- Spillover of Rat Hepatitis E Virus into Humans: An Emerging Zoonosis?Future virology · 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
- Research Progress on Hepatitis E Virus Culture.Pathogens (Basel, Switzerland) · 2025Review
- Effect of Hepatitis E Virus on the Male Reproductive System: A Review of Current Evidence.Viruses · 2025Review
- Current knowledge on the epidemiology and detection methods of hepatitis E virus in China.Virology journal · 2024Review
85 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatitis E virus (HEV) causes acute hepatitis in many parts of the world including Asia, Africa and Latin America. Though self-limiting in normal individuals, it results in ~30% mortality in infected pregnant women. It has also been reported to cause acute and chronic hepatitis in organ transplant patients. Of the seven viral genotypes, genotype-1 virus infects humans and is a major public health concern in South Asian countries. Sporadic cases of genotype-3 and 4 infection in human and animals such as pigs, deer, mongeese have been reported primarily from industrialized countries. Genotype-5, 6 and 7 viruses are known to infect animals such as wild boar and camel, respectively. Genotype-3 and 4 viruses have been successfully propagated in the laboratory in mammalian cell culture. However, genotype-1 virus replicates poorly in mammalian cell culture and no other efficient model exists to study its life cycle. Here, we report that endoplasmic reticulum (ER) stress promotes genotype-1 HEV replication by inducing cap-independent, internal initiation mediated translation of a novel viral protein (named ORF4). Importantly, ORF4 expression and stimulatory effect of ER stress inducers on viral replication is specific to genotype-1. ORF4 protein sequence is mostly conserved among genotype-1 HEV isolates and ORF4 specific antibodies were detected in genotype-1 HEV patient serum. ORF4 interacted with multiple viral and host proteins and assembled a protein complex consisting of viral helicase, RNA dependent RNA polymerase (RdRp), X, host eEF1α1 (eukaryotic elongation factor 1 isoform-1) and tubulinβ. In association with eEF1α1, ORF4 stimulated viral RdRp activity. Furthermore, human hepatoma cells that stably express ORF4 or engineered proteasome resistant ORF4 mutant genome permitted enhanced viral replication. These findings reveal a positive role of ER stress in promoting genotype-1 HEV replication and pave the way towards development of an efficient model of the virus.
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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.