Evidence map›Paper›PMID 35055105›Full record

ArticleInternational journal of molecular sciences2022

Domain 2 of Hepatitis C Virus Protein NS5A Activates Glucokinase and Induces Lipogenesis in Hepatocytes.

Laure Perrin-Cocon, Cindy Kundlacz, Clémence Jacquemin, Xavier Hanoulle, Anne Aublin-Gex, Marianne Figl, Jeremy Manteca, Patrice André, Pierre-Olivier Vidalain, Vincent Lotteau and 1 more

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

14 citing papers in PubMed, 16 citations in OpenAlex.

  1. HBV/HCV coinfection and anti-tuberculosis drug-induced liver injury: from risk assessment and exploration of mechanisms to preventive considerations.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026
    Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. After the Storm: Persistent Molecular Alterations Following HCV Cure.International journal of molecular sciences · 2024
    Review
  10. Talk to Me-Interplay between Mitochondria and Microbiota in Aging.International journal of molecular sciences · 2023
    Review
  11. Article
  12. Review
  13. Hepatitis A Virus Infection and Molecular Research.International journal of molecular sciences · 2022
    Article
  14. Review
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

11 authors at 2 institutions in 1 country.

Laure Perrin-CoconCIRI, Centre International de Recherche en Infectiologie, VIRal Infection Metabolism Immunity Team, University of Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 21 Avenue Tony Garnier, F-69007 Lyon, France.ORCID 0000-0003-0501-6733
Cindy KundlaczCIRI, Centre International de Recherche en Infectiologie, VIRal Infection Metabolism Immunity Team, University of Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 21 Avenue Tony Garnier, F-69007 Lyon, France.ORCID 0000-0001-9398-7200
Clémence JacqueminCIRI, Centre International de Recherche en Infectiologie, VIRal Infection Metabolism Immunity Team, University of Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 21 Avenue Tony Garnier, F-69007 Lyon, France.
Xavier HanoulleCNRS ERL9002-BSI-Integrative Structural Biology, 1 rue du Professeur Calmette, F-59019 Lille, France.ORCID 0000-0002-3755-2680
Anne Aublin-GexCIRI, Centre International de Recherche en Infectiologie, VIRal Infection Metabolism Immunity Team, University of Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 21 Avenue Tony Garnier, F-69007 Lyon, France.
Marianne FiglCIRI, Centre International de Recherche en Infectiologie, VIRal Infection Metabolism Immunity Team, University of Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 21 Avenue Tony Garnier, F-69007 Lyon, France.
Jeremy MantecaCIRI, Centre International de Recherche en Infectiologie, VIRal Infection Metabolism Immunity Team, University of Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 21 Avenue Tony Garnier, F-69007 Lyon, France.
Patrice AndréCIRI, Centre International de Recherche en Infectiologie, VIRal Infection Metabolism Immunity Team, University of Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 21 Avenue Tony Garnier, F-69007 Lyon, France.ORCID 0000-0002-5834-7395
Pierre-Olivier VidalainCIRI, Centre International de Recherche en Infectiologie, VIRal Infection Metabolism Immunity Team, University of Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 21 Avenue Tony Garnier, F-69007 Lyon, France.ORCID 0000-0003-3082-7407
Vincent LotteauCIRI, Centre International de Recherche en Infectiologie, VIRal Infection Metabolism Immunity Team, University of Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 21 Avenue Tony Garnier, F-69007 Lyon, France.ORCID 0000-0003-0997-3282
Olivier DiazCIRI, Centre International de Recherche en Infectiologie, VIRal Infection Metabolism Immunity Team, University of Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, 21 Avenue Tony Garnier, F-69007 Lyon, France.ORCID 0000-0002-3451-9914
Université Claude Bernard Lyon 1 · FRCentre National de la Recherche Scientifique · FR

Funding

Agence Nationale de Recherches sur le Sida et les Hépatites Virales ASA21007CRAFondation pour la Recherche Médicale DEQ20160334893
6 · The paper itself

Abstract

Hepatitis C virus (HCV) relies on cellular lipid metabolism for its replication, and actively modulates lipogenesis and lipid trafficking in infected hepatocytes. This translates into an intracellular accumulation of triglycerides leading to liver steatosis, cirrhosis and hepatocellular carcinoma, which are hallmarks of HCV pathogenesis. While the interaction of HCV with hepatocyte metabolic pathways is patent, how viral proteins are able to redirect central carbon metabolism towards lipogenesis is unclear. Here, we report that the HCV protein NS5A activates the glucokinase (GCK) isoenzyme of hexokinases through its D2 domain (NS5A-D2). GCK is the first rate-limiting enzyme of glycolysis in normal hepatocytes whose expression is replaced by the hexokinase 2 (HK2) isoenzyme in hepatocellular carcinoma cell lines. We took advantage of a unique cellular model specifically engineered to re-express GCK instead of HK2 in the Huh7 cell line to evaluate the consequences of NS5A-D2 expression on central carbon and lipid metabolism. NS5A-D2 increased glucose consumption but decreased glycogen storage. This was accompanied by an altered mitochondrial respiration, an accumulation of intracellular triglycerides and an increased production of very-low density lipoproteins. Altogether, our results show that NS5A-D2 can reprogram central carbon metabolism towards a more energetic and glycolytic phenotype compatible with HCV needs for replication.

Indexed as

Cell Line, TumorGene Knockdown TechniquesGlucokinaseGlycogenGlycolysisHepacivirusHepatitis CHepatocytesHost-Pathogen InteractionsHumansLipid MetabolismLipogenesisMitochondriaProtein BindingProtein Interaction Domains and MotifsRNA-Dependent RNA PolymeraseGlucokinaseGlycogenNS-5 protein, hepatitis C virusRNA-Dependent RNA PolymeraseViral Nonstructural Proteinscentral carbon metabolismglucokinaseglycolysishepatitis C virushepatocytehuman lipoproteinlipogenesisNS5A

Identifiers

PMID35055105
PMCPMC8780509
OpenAlexW4205733296

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.