Evidence map›Paper›PMID 32641492›Full record

ArticleThe Journal of biological chemistry2020

Hepatitis C virus NS3-4A protease regulates the lipid environment for RNA replication by cleaving host enzyme 24-dehydrocholesterol reductase.

Lorillee Tallorin, Valerie A Villareal, Chih-Yun Hsia, Mary A Rodgers, Dominique J Burri, Marc-Philipp Pfeil, Paula Montero Llopis, Brett D Lindenbach, Priscilla L Yang

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

Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

9 citing papers in PubMed, 16 citations in OpenAlex.

  1. HCV NS3/4A protease relocalizes CCTα to viral replication sites, enhancing phosphatidylcholine synthesis and viral replication.Proceedings of the National Academy of Sciences of the United States of America · 2025
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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

9 authors at 2 institutions in 1 country.

Lorillee TallorinDepartment of Microbiology and Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, USA.
Valerie A VillarealDepartment of Microbiology and Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, USA.
Chih-Yun HsiaDepartment of Microbiology and Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, USA.
Mary A RodgersDepartment of Microbiology and Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, USA.
Dominique J BurriDepartment of Microbiology and Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, USA.
Marc-Philipp PfeilDepartment of Microbiology and Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, USA.
Paula Montero LlopisDepartment of Microbiology and Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, USA.
Brett D LindenbachDepartment of Microbial Pathogenesis, Yale Medical School, New Haven, Connecticut, USA.
Priscilla L YangDepartment of Microbiology and Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, USA priscilla_yang@hms.harvard.edu.ORCID 0000-0001-7456-2557
Harvard University · USYale University · US

Funding

MOLECULAR BASIS OF VIRAL INFECTIVITYT32AI007245 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Aaron Gregory Schmidt · 1985 to 2026
$11.3M
Molecular determinants of hepatitis C virus assemblyR01AI087925 · NIAID · YALE UNIVERSITY · PI LINDENBACH, BRETT D. · 2010 to 2020
$4.1M
Hepatitis C virus genome structure: dynamic roles in replication and infectivityR01AI131518 · NIAID · YALE UNIVERSITY · PI LINDENBACH, BRETT D., PYLE, ANNA MARIE · 2017 to 2020
$2.3M
Function and mechanism of the HCV p7 channel and its therapeutic potentialR01GM116898 · NIGMS · HARVARD MEDICAL SCHOOL · PI CHOU, JAMES JEIWEN · 2016 to 2019
$1.9M
How Hepatitis C Virus Regulates Desmosterol to Affect RNA Replication: a New Virus-Host InteractionR21AI148972 · NIAID · STANFORD UNIVERSITY · PI YANG, PRISCILLA LI-NING · 2020 to 2021
$448k
Mechanistic Studies of the Function of Desmosterol Homeostasis in HCV ReplicationF32AI106178 · NIAID · HARVARD MEDICAL SCHOOL · PI VILLAREAL, VALERIE ANNE AGUSTINO · 2013 to 2015
$151k
NIAID NIH HHS F32 AI106178NIAID NIH HHS R01 AI087925NIAID NIH HHS R01 AI131518NIAID NIH HHS R21 AI148972NIAID NIH HHS T32 AI007245NIGMS NIH HHS R01 GM116898
6 · The paper itself

Abstract

Many RNA viruses create specialized membranes for genome replication by manipulating host lipid metabolism and trafficking, but in most cases, we do not know the molecular mechanisms responsible or how specific lipids may impact the associated membrane and viral process. For example, hepatitis C virus (HCV) causes a specific, large-fold increase in the steady-state abundance of intracellular desmosterol, an immediate precursor of cholesterol, resulting in increased fluidity of the membrane where HCV RNA replication occurs. Here, we establish the mechanism responsible for HCV's effect on intracellular desmosterol, whereby the HCV NS3-4A protease controls activity of 24-dehydrocholesterol reductase (DHCR24), the enzyme that catalyzes conversion of desmosterol to cholesterol. Our cumulative evidence for the proposed mechanism includes immunofluorescence microscopy experiments showing co-occurrence of DHCR24 and HCV NS3-4A protease; formation of an additional, faster-migrating DHCR24 species (DHCR24*) in cells harboring a HCV subgenomic replicon RNA or ectopically expressing NS3-4A; and biochemical evidence that NS3-4A cleaves DHCR24 to produce DHCR24*

Indexed as

Lipid MetabolismProteolysisCell Line, TumorHepacivirusHumansMembrane LipidsNerve Tissue ProteinsOxidoreductases Acting on CH-CH Group DonorsRNA, ViralSerine ProteasesViral Nonstructural ProteinsDHCR24 protein, humanMembrane LipidsNerve Tissue ProteinsNS3-4A serine protease, Hepatitis C virusOxidoreductases Acting on CH-CH Group DonorsRNA, ViralSerine ProteasesViral Nonstructural Proteinscholesterol metabolismdesmosterolhepatitis C virus (HCV)host–pathogen interactionlipid environmentmembrane lipidmembrane remodelingpost-translational modification (PTM)RNA replicationviral proteaseviral replication

Identifiers

PMID32641492
PMCPMC7458815
OpenAlexW3040697948

What OpenQuestion holds

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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.