ArticlePLoS pathogens2020
Identification of functional cis-acting RNA elements in the hepatitis E virus genome required for viral replication.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- GRP75 blocks hepatitis E virus infection by targeting HEV-ORF2 for degradation through chaperone-mediated autophagy and promoting IRF3 activation.Journal of virology · 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
- 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
- Cell binding tropism of rat hepatitis E virus is a pivotal determinant of its zoonotic transmission to humans.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Combining RNA Interference and RIG-I Activation to Inhibit Hepatitis E Virus Replication.Viruses · 2024Article
- Article
- 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
- Article
- The PRMT5/WDR77 complex restricts hepatitis E virus replication.PLoS pathogens · 2023Article
- Hepatitis E Virus Life Cycle.Advances in experimental medicine and biology · 2023Article
- Structural aspects of hepatitis E virus.Archives of virology · 2022Review
- Two mutations in the ORF1 of genotype 1 hepatitis E virus enhance virus replication and may associate with fulminant hepatic failure.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- The Capsid (ORF2) Protein of Hepatitis E Virus in Feces Is C-Terminally Truncated.Pathogens (Basel, Switzerland) · 2021Article
- Open reading frame 3 protein of hepatitis E virus: Multi-function protein with endless potential.World journal of gastroenterology · 2021Review
- A broadly neutralizing monoclonal antibody induces broad protection against heterogeneous PRRSV strains in piglets.Veterinary research · 2021Article
- A novel cell culture system modeling the SARS-CoV-2 life cycle.PLoS pathogens · 2021Article
- Dynamics of Hepatitis E Virus (HEV) Antibodies and Development of a Multifactorial Model To Improve the Diagnosis of HEV Infection in Resource-Limited Settings.Journal of clinical microbiology · 2021Article
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 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There are approximately 20 million events of hepatitis E virus (HEV) infection worldwide annually. The genome of HEV is a single-strand, positive-sense RNA containing 5' and 3' untranslated regions and three open reading frames (ORF). HEV genome has 5' cap and 3' poly(A) tail to mimic host mRNA to escape the host innate immune surveillance and utilize host translational machineries for viral protein translation. The replication mechanism of HEV is poorly understood, especially how the viral polymerase distinguishes viral RNA from host mRNA to synthesize new viral genomes. We hypothesize that the HEV genome contains cis-acting elements that can be recognized by the virally encoded polymerase as "self" for replication. To identify functional cis-acting elements systematically across the HEV genome, we utilized an ORF1 transcomplementation system. Ultimately, we found two highly conserved cis-acting RNA elements within the ORF1 and ORF2 coding regions that are required for viral genome replication in a diverse panel of HEV genotypes. Synonymous mutations in the cis-acting RNA elements, not altering the ORF1 and ORF2 protein sequences, significantly impaired production of infectious viral particles. Mechanistic studies revealed that the cis-acting elements form secondary structures needed to interact with the HEV ORF1 protein to promote HEV replication. Thus, these cis-acting elements function as a scaffold, providing a specific "signal" that recruits viral and host factors to assemble the viral replication complex. Altogether, this work not only facilitates our understanding of the HEV life cycle and provides novel, RNA-directed targets for potential HEV treatments, but also sheds light on the development of HEV as a therapeutic delivery vector.
Indexed as
Identifiers
What OpenQuestion holds
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.