Evidence map›Paper›PMID 22593157›Full record

ArticleJournal of virology2012

Structural analysis of hepatitis C virus core-E1 signal peptide and requirements for cleavage of the genotype 3a signal sequence by signal peptide peptidase.

Verena Oehler, Ana Filipe, Roland Montserret, Daniel da Costa, Gaie Brown, François Penin, John McLauchlan

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.3field-weighted citation impact, top 19% 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

12 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Review
  3. Bioinformatics Analysis of Domain 1 of HCV-Core Protein: Iran.International journal of peptide research and therapeutics · 2020
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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 3 institutions in 2 countries.

Verena OehlerMRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
Ana Filipe
Roland Montserret
Daniel da Costa
Gaie Brown
François Penin
John McLauchlan
MRC University of Glasgow Centre for Virus Research · GBCentre National de la Recherche Scientifique · FRStructural and Molecular Basis of Infectious Systems · FR

Funding

Medical Research Council G0801769
6 · The paper itself

Abstract

The maturation of the hepatitis C virus (HCV) core protein requires proteolytic processing by two host proteases: signal peptidase (SP) and the intramembrane-cleaving protease signal peptide peptidase (SPP). Previous work on HCV genotype 1a (GT1a) and GT2a has identified crucial residues required for efficient signal peptide processing by SPP, which in turn has an effect on the production of infectious virus particles. Here we demonstrate that the JFH1 GT2a core-E1 signal peptide can be adapted to the GT3a sequence without affecting the production of infectious HCV. Through mutagenesis studies, we identified crucial residues required for core-E1 signal peptide processing, including a GT3a sequence-specific histidine (His) at position 187. In addition, the stable knockdown of intracellular SPP levels in HuH-7 cells significantly affects HCV virus titers, further demonstrating the requirement for SPP for the maturation of core and the production of infectious HCV particles. Finally, our nuclear magnetic resonance (NMR) structural analysis of a synthetic HCV JFH1 GT2a core-E1 signal peptide provides an essential structural template for a further understanding of core processing as well as the first model for an SPP substrate within its membrane environment. Our findings give deeper insights into the mechanisms of intramembrane-cleaving proteases and the impact on viral infections.

Indexed as

Protein Sorting SignalsAspartic Acid EndopeptidasesHEK293 CellsHepacivirusHepatitis CHumansMutagenesisNuclear Magnetic Resonance, BiomolecularViral Core ProteinsAspartic Acid EndopeptidasesProtein Sorting Signalssignal peptide peptidaseViral Core Proteins

Identifiers

PMID22593157
PMCPMC3421639
OpenAlexW2135115422

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.