Evidence map›Paper›PMID 30726741›Full record

ArticleCell reports2019

Flavivirus NS1 Triggers Tissue-Specific Vascular Endothelial Dysfunction Reflecting Disease Tropism.

Henry Puerta-Guardo, Dustin R Glasner, Diego A Espinosa, Scott B Biering, Mark Patana, Kalani Ratnasiri, Chunling Wang, P Robert Beatty, Eva Harris

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 199 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
199citing papers in PubMed, 1 pooled it
34.4field-weighted citation impact, top 1% 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

199 citing papers in PubMed, 1 synthesis or guideline pooled it, 318 citations in OpenAlex.

  1. Pooled it
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  5. Review
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  8. Article
  9. Secreted Nonstructural Protein 3 is a Pathogenic Determinant of Orbivirus.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
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139 more citing papers are in PubMed but not listed here.

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 1 institution in 1 country.

Henry Puerta-GuardoDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
Dustin R GlasnerDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
Diego A EspinosaDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
Scott B BieringDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
Mark PatanaDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
Kalani RatnasiriDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
Chunling WangDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
P Robert BeattyDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
Eva HarrisDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA. Electronic address: eharris@berkeley.edu.
University of California, Berkeley · US

Funding

Dissecting novel mechanisms of dengue virus NS1-induced vascular leakR01AI124493 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI HARRIS, EVA · 2016 to 2020
$1.9M
NIAID NIH HHS R01 AI124493
6 · The paper itself

Abstract

Flaviviruses cause systemic or neurotropic-encephalitic pathology in humans. The flavivirus nonstructural protein 1 (NS1) is a secreted glycoprotein involved in viral replication, immune evasion, and vascular leakage during dengue virus infection. However, the contribution of secreted NS1 from related flaviviruses to viral pathogenesis remains unknown. Here, we demonstrate that NS1 from dengue, Zika, West Nile, Japanese encephalitis, and yellow fever viruses selectively binds to and alters permeability of human endothelial cells from lung, dermis, umbilical vein, brain, and liver in vitro and causes tissue-specific vascular leakage in mice, reflecting the pathophysiology of each flavivirus. Mechanistically, each flavivirus NS1 leads to differential disruption of endothelial glycocalyx components, resulting in endothelial hyperpermeability. Our findings reveal the capacity of a secreted viral protein to modulate endothelial barrier function in a tissue-specific manner both in vitro and in vivo, potentially influencing virus dissemination and pathogenesis and providing targets for antiviral therapies and vaccine development.

Indexed as

AnimalsBrainCell LineCell Membrane PermeabilityDengueDengue VirusDermisEncephalitis Virus, JapaneseEndothelial CellsGene ExpressionGlycocalyxHumansLiverLungMaleMiceNS1 protein, FlavivirusViral Nonstructural Proteinsdengue virusdisease tropismendothelial permeabilityFlavivirusJapanese encephalitis virusNS1vascular leakWest Nile virusyellow fever virusZika virus

Identifiers

PMID30726741
PMCPMC6934102
OpenAlexW2912089311

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.