Evidence map›Paper›PMID 34346770›Full record

ArticleJournal of virology2021

Levels of Circulating NS1 Impact West Nile Virus Spread to the Brain.

Alex W Wessel, Kimberly A Dowd, Scott B Biering, Ping Zhang, Melissa A Edeling, Christopher A Nelson, Kristen E Funk, Christina R DeMaso, Robyn S Klein, Janet L Smith and 6 more

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

16 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. 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

16 authors at 6 institutions in 2 countries.

Alex W WesselDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
Kimberly A DowdViral Pathogenesis Section, National Institute of Allergy and Infectious Diseases, National Institutes of Healthgrid.94365.3d, Bethesda, Maryland, USA.
Scott B BieringDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeleygrid.47840.3f, Berkeley, California, USA.
Ping ZhangDepartment of Immunology, Key Laboratory of Tropical Diseases Control, Zhongshan School of Medicine, Sun Yat-sen Universitygrid.12981.33, Guangzhou, China.
Melissa A EdelingDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
Christopher A NelsonDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
Kristen E FunkDepartment of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Christina R DeMasoViral Pathogenesis Section, National Institute of Allergy and Infectious Diseases, National Institutes of Healthgrid.94365.3d, Bethesda, Maryland, USA.
Robyn S KleinDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
Janet L SmithLife Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA.
Thu Minh CaoDepartment of Biological Sciences, Purdue University, West Lafayette, Indiana, USA.
Richard J KuhnDepartment of Biological Sciences, Purdue University, West Lafayette, Indiana, USA.
Daved H FremontDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.ORCID 0000-0002-8544-2689
Eva HarrisDivision of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeleygrid.47840.3f, Berkeley, California, USA.
Theodore C PiersonViral Pathogenesis Section, National Institute of Allergy and Infectious Diseases, National Institutes of Healthgrid.94365.3d, Bethesda, Maryland, USA.
Michael S DiamondDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.ORCID 0000-0002-8791-3165
Washington University in St. Louis · USNational Institutes of Health · USPurdue University West Lafayette · USUniversity of California, Berkeley · USSun Yat-sen University · CNUniversity of Michigan · US

Funding

The humoral response to Zika virus infection and vaccinationZIAAI001209 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI PIERSON, THEODORE · 2016 to 2025
$22.0M
Infectious Diseases/Basic Microbial Pathogenic MechanismsT32AI007172 · NIAID · WASHINGTON UNIVERSITY · PI Daniel E. Goldberg, JENNIFER A PHILIPS · 1985 to 2026
$13.0M
COVID Supplement B Cell Epitope Discovery and Mechanisms of Antibody Protection.75N93019C00062 · NIAID · WASHINGTON UNIVERSITY · PI FREMONT, DAVED · 2019 to 2023
$11.7M
Antibody-based Protection against FlavivirsesR01AI073755 · NIAID · WASHINGTON UNIVERSITY · PI DIAMOND, MICHAEL S, FREMONT, DAVED H. · 2007 to 2022
$11.4M
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 75N93019C00062NIAID NIH HHS HHSN272201400058CNIAID NIH HHS HHSN272201700060CNIAID NIH HHS R01 AI073755NIAID NIH HHS R01 AI124493NIAID NIH HHS T32 AI007172
6 · The paper itself

Abstract

Dengue virus (DENV) and West Nile virus (WNV) are arthropod-transmitted flaviviruses that cause systemic vascular leakage and encephalitis syndromes, respectively, in humans. However, the viral factors contributing to these specific clinical disorders are not completely understood. Flavivirus nonstructural protein 1 (NS1) is required for replication, expressed on the cell surface, and secreted as a soluble glycoprotein, reaching high levels in the blood of infected individuals. Extracellular DENV NS1 and WNV NS1 interact with host proteins and cells, have immune evasion functions, and promote endothelial dysfunction in a tissue-specific manner. To characterize how differences in DENV NS1 and WNV NS1 might function in pathogenesis, we generated WNV NS1 variants with substitutions corresponding to residues found in DENV NS1. We discovered that the substitution NS1-P101K led to reduced WNV infectivity in the brain and attenuated lethality in infected mice, although the virus replicated efficiently in cell culture and peripheral organs and bound at wild-type levels to brain endothelial cells and complement components. The P101K substitution resulted in reduced NS1 antigenemia in mice, and this was associated with reduced WNV spread to the brain. Because exogenous administration of NS1 protein rescued WNV brain infectivity in mice, we conclude that circulating WNV NS1 facilitates viral dissemination into the central nervous system and impacts disease outcomes.

Indexed as

AnimalsBrainDengue VirusEndothelial CellsFemaleFlavivirusImmune EvasionMaleMiceMice, Inbred C57BLViral Nonstructural ProteinsVirus ReplicationWest Nile FeverWest Nile virusnonstructural protein 1, West Nile virusNS1 protein, dengue-1 virusViral Nonstructural Proteinsanimal modeldisseminationendothelial cellsflavivirusviral pathogenesisvirology

Identifiers

PMID34346770
PMCPMC8475509
OpenAlexW3192039125

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.