Evidence map›Paper›PMID 34387882›Full record

ArticleHepatology (Baltimore, Md.)2022

Hepatitis E virus RNA-dependent RNA polymerase is involved in RNA replication and infectious particle production.

Noémie Oechslin, Nathalie Da Silva, Dagmara Szkolnicka, François-Xavier Cantrelle, Xavier Hanoulle, Darius Moradpour, Jérôme Gouttenoire

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Hepatology (Baltimore, Md.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.5field-weighted citation impact, top 16% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. 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 · 2023
    Article
  6. Article
  7. Review
  8. Article
  9. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Noémie OechslinDivision of Gastroenterology and Hepatology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Nathalie Da SilvaDivision of Gastroenterology and Hepatology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Dagmara SzkolnickaDivision of Gastroenterology and Hepatology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
François-Xavier CantrelleUMR1167, University of Lille, INSERM, Lille University Hospital, Institut Pasteur de Lille, Lille, France.
Xavier HanoulleUMR1167, University of Lille, INSERM, Lille University Hospital, Institut Pasteur de Lille, Lille, France.
Darius MoradpourDivision of Gastroenterology and Hepatology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.ORCID 0000-0003-1977-6792
Jérôme GouttenoireDivision of Gastroenterology and Hepatology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.ORCID 0000-0002-7715-1494
University of Lausanne · CHCentre National de la Recherche Scientifique · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

aimsHepatitis E virus (HEV) is one of the most common causes of acute hepatitis worldwide. Its positive-strand RNA genome encodes three open reading frames (ORF). ORF1 is translated into a large protein composed of multiple domains and is known as the viral replicase. The RNA-dependent RNA polymerase (RDRP) domain is responsible for the synthesis of viral RNA. APPROACH AND

resultsHere, we identified a highly conserved α-helix located in the RDRP thumb subdomain. Nuclear magnetic resonance demonstrated an amphipathic α-helix extending from amino acids 1628 to 1644 of the ORF1 protein. Functional analyses revealed a dual role of this helix in HEV RNA replication and virus production, including assembly and release. Mutations on the hydrophobic side of the amphipathic α-helix impaired RNA replication and resulted in the selection of a second-site compensatory change in the RDRP palm subdomain. Other mutations enhanced RNA replication but impaired virus assembly and/or release.

conclusionsStructure-function analyses identified a conserved amphipathic α-helix in the thumb subdomain of the HEV RDRP with a dual role in viral RNA replication and infectious particle production. This study provides structural insights into a key segment of the ORF1 protein and describes the successful use of reverse genetics in HEV, revealing functional interactions between the RDRP thumb and palm subdomains. On a broader scale, it demonstrates that the HEV replicase, similar to those of other positive-strand RNA viruses, is also involved in virus production.

Indexed as

Hepatitis EHepatitis E virusHep G2 CellsHumansMutationProtein Conformation, alpha-HelicalRNA-Dependent RNA PolymeraseRNA, ViralStructure-Activity RelationshipVirus ReplicationRNA-Dependent RNA PolymeraseRNA, Viral

Identifiers

PMID34387882
PMCPMC9300124
OpenAlexW3190214202

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.