Evidence map›Paper›PMID 32291299›Full record

ArticlemBio2020

A Sensitive Yellow Fever Virus Entry Reporter Identifies Valosin-Containing Protein (VCP/p97) as an Essential Host Factor for Flavivirus Uncoating.

Harish N Ramanathan, Shuo Zhang, Florian Douam, Katrina B Mar, Jinhong Chang, Priscilla L Yang, John W Schoggins, Alexander Ploss, Brett D Lindenbach

Open access · goldAbstract read
In one paragraph

Article in mBio, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

32 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
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  6. A trove of antiviral TRIM family E3 ligases in reptiles.bioRxiv : the preprint server for biology · 2025
    Article
  7. Modes of action of a small molecule antiviral compound targeting yellow fever virus NS4B protein.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  8. Review
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  13. Review
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  19. Review
  20. Pathogenesis of Zika Virus Infection.Annual review of pathology · 2023
    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

9 authors at 5 institutions in 1 country.

Harish N RamanathanDepartment of Microbial Pathogenesis, Yale University, New Haven, Connecticut, USA.
Shuo ZhangDepartment of Microbial Pathogenesis, Yale University, New Haven, Connecticut, USA.
Florian DouamDepartment of Molecular Biology, Princeton University, Princeton, New Jersey, USA.
Katrina B MarDepartment of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Jinhong ChangDepartment of Experimental Therapeutics, The Baruch S. Blumberg Institute, Doylestown, Pennsylvania, USA.
Priscilla L YangDepartment of Microbiology and the Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, USA.
John W SchogginsDepartment of Microbiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Alexander PlossDepartment of Molecular Biology, Princeton University, Princeton, New Jersey, USA.
Brett D LindenbachDepartment of Microbial Pathogenesis, Yale University, New Haven, Connecticut, USA brett.lindenbach@yale.edu.
Yale University · USPrinceton University · USThe University of Texas Southwestern Medical Center · USBaruch S. Blumberg Institute · USBoston VA Research Institute · US

Funding

INTEGRATIVE IMMUNOLOGY TRAINING PROGRAMT32AI005284 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI Nan Yan · 2003 to 2026
$7.4M
Genetic Viral and Host Adaptations to Breach Species Barriers of HCVR01AI107301 · NIAID · PRINCETON UNIVERSITY · PI Thomas Pietschmann, Alexander Ploss · 2013 to 2026
$6.0M
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
Bacterial effectors as probes to study (+) RNA virus-host cell biologyR21AI120113 · NIAID · YALE UNIVERSITY · PI LINDENBACH, BRETT D. · 2015 to 2016
$458k
NIAID NIH HHS R01 AI087925NIAID NIH HHS R01 AI107301NIAID NIH HHS R01 AI131518NIAID NIH HHS R21 AI120113NIAID NIH HHS T32 AI005284Wellcome Trust
6 · The paper itself

Abstract

While the basic mechanisms of flavivirus entry and fusion are understood, little is known about the postfusion events that precede RNA replication, such as nucleocapsid disassembly. We describe here a sensitive, conditionally replication-defective yellow fever virus (YFV) entry reporter, YFVΔSK/Nluc, to quantitively monitor the translation of incoming, virus particle-delivered genomes. We validated that YFVΔSK/Nluc gene expression can be neutralized by YFV-specific antisera and requires known flavivirus entry pathways and cellular factors, including clathrin- and dynamin-mediated endocytosis, endosomal acidification, YFV E glycoprotein-mediated fusion, and cellular LY6E and RPLP1 expression. The initial round of YFV translation was shown to require cellular ubiquitylation, consistent with recent findings that dengue virus capsid protein must be ubiquitylated in order for nucleocapsid uncoating to occur. Importantly, translation of incoming YFV genomes also required valosin-containing protein (VCP)/p97, a cellular ATPase that unfolds and extracts ubiquitylated client proteins from large complexes. RNA transfection and washout experiments showed that VCP/p97 functions at a postfusion, pretranslation step in YFV entry. Finally, VCP/p97 activity was required by other flaviviruses in mammalian cells and by YFV in mosquito cells. Together, these data support a critical role for VCP/p97 in the disassembly of incoming flavivirus nucleocapsids during a postfusion step in virus entry.

Indexed as

Virus UncoatingAnimalsCell LineCricetinaeFemaleGenes, ReporterGenome, ViralHEK293 CellsHeLa CellsHumansKidneyMiceMice, Inbred C57BLValosin Containing ProteinVirus InternalizationVirus ReplicationValosin Containing ProteinVCP protein, humanflavivirusnucleocapsiduncoatingviral entry

Identifiers

PMID32291299
PMCPMC7157815
OpenAlexW3015995564

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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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.