Evidence map›Paper›PMID 36106873›Full record

ArticleJournal of virology2022

Molecular Determinants of Tissue Specificity of Flavivirus Nonstructural Protein 1 Interaction with Endothelial Cells.

Nicholas T N Lo, Susan Z Roodsari, Nicole L Tin, Marcus P Wong, Scott B Biering, Eva Harris

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
4.8field-weighted citation impact, top 4% 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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Dengue Virus NS1 Binds Ephrin B1 to Trigger Endothelial Dysfunction.bioRxiv : the preprint server for biology · 2025
    Article
  9. Article
  10. Viruses · 2025
    Article
  11. Article
  12. Article
  13. Extracellular Vesicles inInternational journal of molecular sciences · 2024
    Review
  14. Severe dengue in the intensive care unit.Journal of intensive medicine · 2024
    Review
  15. Review
  16. Article
  17. Review
  18. Article
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

6 authors at 1 institution in 1 country.

Nicholas T N LoDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, grid.47840.3fBerkeley, California, USA.ORCID 0000-0002-4289-1222
Susan Z RoodsariDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, grid.47840.3fBerkeley, California, USA.
Nicole L TinDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, grid.47840.3fBerkeley, California, USA.
Marcus P WongDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, grid.47840.3fBerkeley, California, USA.ORCID 0000-0001-6554-2976
Scott B BieringDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, grid.47840.3fBerkeley, California, USA.ORCID 0000-0003-1991-629X
Eva HarrisDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, grid.47840.3fBerkeley, California, USA.ORCID 0000-0002-7238-4037
University of California, Berkeley · US

Funding

Host factors and viral determinants mediating flavivirus NS1 tissue-specific endothelial dysfunction and vascular leakR01AI168003 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI Eva Harris · 2022 to 2026
$3.2M
Dissecting novel mechanisms of dengue virus NS1-induced vascular leakR01AI124493 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI HARRIS, EVA · 2016 to 2020
$1.9M
HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) AI124493NIAID NIH HHS R01 AI124493NIAID NIH HHS R01 AI168003
6 · The paper itself

Abstract

Members of the mosquito-borne flavivirus genus such as dengue (DENV), West Nile (WNV), and Zika (ZIKV) viruses cause distinct diseases and affect different tissues. We previously found that the secreted flaviviral nonstructural protein 1 (NS1) interacts with endothelial cells and disrupts endothelial barrier function in a tissue-specific manner consistent with the disease tropism of the respective viruses. However, the underlying molecular mechanism of this tissue-specific NS1-endothelial cell interaction is not well understood. To elucidate the distinct role(s) that the wing and β-ladder domains of NS1 play in NS1 interactions with endothelial cells, we constructed flavivirus NS1 chimeras that exchanged the wing and β-ladder domains in a pairwise manner between DENV, WNV, and ZIKV NS1. We found that both the NS1 wing and β-ladder domains conferred NS1 tissue-specific endothelial dysfunction, with the wing conferring cell binding and the β-ladder involved in inducing endothelial hyperpermeability as measured by transendothelial electrical resistance. To narrow down the amino acids dictating cell binding specificity, we utilized the DENV-WNV NS1 chimera and identified residues 91 to 93 (GDI) of DENV NS1 as a molecular motif determining binding specificity. Further, using an

Indexed as

Endothelial CellsFlavivirusViral Nonstructural ProteinsViral TropismAmino AcidsAnimalsAntiviral AgentsCell CommunicationDengue VirusFlavivirus InfectionsMiceWest Nile virusZika VirusAmino AcidsAntiviral AgentsViral Nonstructural Proteinsdengue virusendothelial dysfunctionflavivirusNS1tissue specificityvascular leak

Identifiers

PMID36106873
PMCPMC9555157
OpenAlexW4295907500

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.