Evidence map›Paper›PMID 22553322›Full record

ArticleJournal of virology2012

Evidence for a genetic and physical interaction between nonstructural proteins NS1 and NS4B that modulates replication of West Nile virus.

Soonjeon Youn, Tuo Li, Broc T McCune, Melissa A Edeling, Daved H Fremont, Ileana M Cristea, Michael S Diamond

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers.

0numbers the graph read from it
0cells of the map it votes in
116citing papers in PubMed
13.5field-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

116 citing papers in PubMed, 177 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. AlphaFold Prediction of Protein-Protein Interactions in theInternational journal of molecular sciences · 2025
    Article
  12. Review
  13. Article
  14. Review
  15. 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
  16. Review
  17. Article
  18. Mechanistic insights into dengue virus inhibition by a clinical trial compound NITD-688.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  19. Functional Roles and Host Interactions ofPathogens (Basel, Switzerland) · 2025
    Review
  20. Article

56 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

7 authors at 2 institutions in 1 country.

Soonjeon YounDepartment of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Tuo Li
Broc T McCune
Melissa A Edeling
Daved H Fremont
Ileana M Cristea
Michael S Diamond
Washington University in St. Louis · USPrinceton University · US

Funding

Virology and Smallpox VaccinationsU54AI057160 · NIAID · WASHINGTON UNIVERSITY · PI RAY, RANJIT · 2003 to 2013
$80.9M
MOLECULAR ONCOLOGY TRAINING GRANTT32CA113275 · NCI · WASHINGTON UNIVERSITY · PI Matthew J Walter · 2006 to 2026
$5.7M
Proteomic Tools to Uncover the Role of Chromatin Remodeling in HIV-1 InfectionDP1DA026192 · NIDA · PRINCETON UNIVERSITY · PI CRISTEA, ILEANA M. · 2008 to 2012
$3.9M
NCI NIH HHS T32 CA113275NIAID NIH HHS U54 AI057160NIAID NIH HHS U54-AI057160NIDA NIH HHS DP1 DA026192NIDA NIH HHS DP1DA026192
6 · The paper itself

Abstract

Flavivirus NS1 is a nonstructural glycoprotein that is expressed on the cell surface and secreted into the extracellular space. Despite its transit through the secretory pathway, NS1 is an essential gene linked to early viral RNA replication. How this occurs has remained a mystery given the disparate localization of NS1 and the viral RNA replication complex, as the latter is present on the cytosolic face of the endoplasmic reticulum (ER). We recently identified an N-terminal di-amino acid motif in NS1 that modulates protein targeting and affected viral replication. Exchange of two amino acids at positions 10 and 11 from dengue virus (DENV) into West Nile virus (WNV) NS1 (RQ10NK) changed its relative surface expression and secretion and attenuated infectivity. However, the phenotype of WNV containing NS1 RQ10NK was unstable, as within two passages heterogeneous plaque variants were observed. Here, using a mutant WNV encoding the NS1 RQ10NK mutation, we identified a suppressor mutation (F86C) in NS4B, a virally encoded transmembrane protein with loops on both the luminal and cytoplasmic sides of the ER membrane. Introduction of NS4B F86C specifically rescued RNA replication of mutant WNV but did not affect the wild-type virus. Mass spectrometry and coimmunoprecipitation studies established a novel physical interaction between NS1 and NS4B, suggesting a mechanism for how luminal NS1 conveys signals to the cytoplasm to regulate RNA replication.

Indexed as

Protein Interaction MappingVirus ReplicationAmino Acid SubstitutionAnimalsCell LineCricetinaeImmunoprecipitationMass SpectrometryMutant ProteinsMutation, MissenseProtein BindingSuppression, GeneticViral Nonstructural ProteinsWest Nile virusMutant Proteinsnonstructural protein 1, West Nile virusNS4B protein, flavivirusViral Nonstructural Proteins

Identifiers

PMID22553322
PMCPMC3416313
OpenAlexW2008216856

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.