Evidence map›Paper›PMID 27575636›Full record

ArticlePLoS pathogens2016

The Dengue Virus NS5 Protein Intrudes in the Cellular Spliceosome and Modulates Splicing.

Federico A De Maio, Guillermo Risso, Nestor G Iglesias, Priya Shah, Berta Pozzi, Leopoldo G Gebhard, Pablo Mammi, Estefania Mancini, Marcelo J Yanovsky, Raul Andino and 3 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.

0numbers the graph read from it
0cells of the map it votes in
124citing papers in PubMed
16.6field-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

124 citing papers in PubMed, 208 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Biosafety and health · 2026
    Article
  6. Article
  7. Cellular Biology: Virus-Host Interactions and RNA Structure and Function.Current topics in microbiology and immunology · 2026
    Review
  8. Article
  9. Viral Modulation of Host Splicing.Annual review of virology · 2025
    Review
  10. AProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Functional Roles and Host Interactions ofPathogens (Basel, Switzerland) · 2025
    Review
  16. Proteomic profiling of pseudorabies virus-infected PK-15 cells based on 4D label free analysis.Veterinary research forum : an international quarterly journal · 2025
    Article
  17. Article
  18. Article
  19. Article
  20. Review

64 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

13 authors at 2 institutions in 2 countries.

Federico A De MaioFundación Instituto Leloir-CONICET, Buenos Aires, Argentina.
Guillermo RissoInstituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE, UBA-CONICET), Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires.
Nestor G IglesiasFundación Instituto Leloir-CONICET, Buenos Aires, Argentina.
Priya ShahDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, California, United States of America.
Berta PozziInstituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE, UBA-CONICET), Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires.
Leopoldo G GebhardFundación Instituto Leloir-CONICET, Buenos Aires, Argentina.
Pablo MammiInstituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE, UBA-CONICET), Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires.
Estefania ManciniFundación Instituto Leloir-CONICET, Buenos Aires, Argentina.ORCID 0000-0002-7308-1273
Marcelo J YanovskyFundación Instituto Leloir-CONICET, Buenos Aires, Argentina.
Raul AndinoDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, California, United States of America.
Nevan KroganDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, California, United States of America.
Anabella SrebrowInstituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE, UBA-CONICET), Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires.
Andrea V GamarnikFundación Instituto Leloir-CONICET, Buenos Aires, Argentina.
Consejo Nacional de Investigaciones Científicas y Técnicas · ARUniversity of California, San Francisco · US

Funding

MECHANISMS OF DENGUE VIRUS GENOME ENCAPSIDATION AND UNCOATINGR01AI095175 · NIAID · FUNDACION INSTITUTO LELOIR · PI GAMARNIK, ANDREA · 2011 to 2020
$1.0M
NIAID NIH HHS R01 AI095175
6 · The paper itself

Abstract

Dengue virus NS5 protein plays multiple functions in the cytoplasm of infected cells, enabling viral RNA replication and counteracting host antiviral responses. Here, we demonstrate a novel function of NS5 in the nucleus where it interferes with cellular splicing. Using global proteomic analysis of infected cells together with functional studies, we found that NS5 binds spliceosome complexes and modulates endogenous splicing as well as minigene-derived alternative splicing patterns. In particular, we show that NS5 alone, or in the context of viral infection, interacts with core components of the U5 snRNP particle, CD2BP2 and DDX23, alters the inclusion/exclusion ratio of alternative splicing events, and changes mRNA isoform abundance of known antiviral factors. Interestingly, a genome wide transcriptome analysis, using recently developed bioinformatics tools, revealed an increase of intron retention upon dengue virus infection, and viral replication was improved by silencing specific U5 components. Different mechanistic studies indicate that binding of NS5 to the spliceosome reduces the efficiency of pre-mRNA processing, independently of NS5 enzymatic activities. We propose that NS5 binding to U5 snRNP proteins hijacks the splicing machinery resulting in a less restrictive environment for viral replication.

Indexed as

DengueRNA SplicingAnimalsCell LineDengue VirusFluorescent Antibody TechniqueHigh-Throughput Nucleotide SequencingHost-Parasite InteractionsHumansPolymerase Chain ReactionRibonucleoprotein, U5 Small NuclearSpliceosomesTransfectionViral Nonstructural ProteinsNS5 protein, dengue virusRibonucleoprotein, U5 Small NuclearViral Nonstructural Proteins

Identifiers

PMID27575636
PMCPMC5004807
OpenAlexW2516001222

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.