Evidence map›Paper›PMID 29167346›Full record

ArticleJournal of virology2018

Glycine Zipper Motifs in Hepatitis C Virus Nonstructural Protein 4B Are Required for the Establishment of Viral Replication Organelles.

David Paul, Vanesa Madan, Omar Ramirez, Maja Bencun, Ina Karen Stoeck, Vlastimil Jirasko, Ralf Bartenschlager

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

13 citing papers in PubMed, 22 citations in OpenAlex.

  1. Review
  2. Article
  3. Hepatitis B virus entry, assembly, and egress.Microbiology and molecular biology reviews : MMBR · 2024
    Review
  4. Review
  5. Article
  6. The role of autophagy in viral infections.Journal of biomedical science · 2023
    Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Hepatitis C Virus Replication.Cold Spring Harbor perspectives in medicine · 2020
    Review
  13. Article
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.

David PaulDepartment of Infectious Diseases, Molecular Virology, Medical Faculty, Heidelberg University, Heidelberg, Germany david.paul@med.uni-heidelberg.de ralf.bartenschlager@med.uni-heidelberg.de.ORCID https://orcid.org/0000-0002-6652-331X
Vanesa MadanDepartment of Infectious Diseases, Molecular Virology, Medical Faculty, Heidelberg University, Heidelberg, Germany.
Omar RamirezDepartment of Neurobiology, Interdisciplinary Center for Neurosciences, Heidelberg University, Heidelberg, Germany.
Maja BencunDepartment of Infectious Diseases, Molecular Virology, Medical Faculty, Heidelberg University, Heidelberg, Germany.
Ina Karen StoeckDepartment of Infectious Diseases, Molecular Virology, Medical Faculty, Heidelberg University, Heidelberg, Germany.
Vlastimil JiraskoPhysical Chemistry, ETH Zurich, Zurich, Switzerland.
Ralf BartenschlagerDepartment of Infectious Diseases, Molecular Virology, Medical Faculty, Heidelberg University, Heidelberg, Germany david.paul@med.uni-heidelberg.de ralf.bartenschlager@med.uni-heidelberg.de.ORCID https://orcid.org/0000-0001-5601-9307
Heidelberg University · DEETH Zurich · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hepatitis C virus (HCV) RNA replication occurs in tight association with remodeled host cell membranes, presenting as cytoplasmic accumulations of single-, double-, and multimembrane vesicles in infected cells. Formation of these so-called replication organelles is mediated by a complex interplay of host cell factors and viral replicase proteins. Of these, nonstructural protein 4B (NS4B), an integral transmembrane protein, appears to play a key role, but little is known about the molecular mechanisms of how this protein contributes to organelle biogenesis. Using forward and reverse genetics, we identified glycine zipper motifs within transmembrane helices 2 and 3 of NS4B that are critically involved in viral RNA replication. Foerster resonance energy transfer analysis revealed the importance of the glycine zippers in NS4B homo- and heterotypic self-interactions. Additionally, ultrastructural analysis using electron microscopy unraveled a prominent role of glycine zipper residues for the subcellular distribution and the morphology of HCV-induced double-membrane vesicles. Notably, loss-of-function NS4B glycine zipper mutants prominently induced single-membrane vesicles with secondary invaginations that might represent an arrested intermediate state in double-membrane vesicle formation. These findings highlight a so-far-unknown role of glycine residues within the membrane integral core domain for NS4B self-interaction and functional as well as structural integrity of HCV replication organelles.

Indexed as

Virus ReplicationCell LineGlycineHepacivirusHepatitis CHumansOrganellesProtein Structure, SecondaryRNA, ViralViral Nonstructural ProteinsGlycineNS4B protein, flavivirusRNA, ViralViral Nonstructural Proteinsglycine zipperhepatitis C virusmembrane proteinsmembranous webNS4Bpositive-strand RNA virusreplication organelle

Identifiers

PMID29167346
PMCPMC5790954
OpenAlexW2768755161

What OpenQuestion holds

Textmetadata
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.