Evidence map›Paper›PMID 29294313›Full record

ArticleVirus research2018

K48-linked polyubiquitination of dengue virus NS1 protein inhibits its interaction with the viral partner NS4B.

Maria Isabel Giraldo, Oscar Vargas-Cuartas, Juan Carlos Gallego-Gomez, Pei-Yong Shi, Leonardo Padilla-Sanabria, Jhon Carlos Castaño-Osorio, Ricardo Rajsbaum

Abstract read
In one paragraph

Article in Virus research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.2field-weighted citation impact, top 11% 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, 27 citations in OpenAlex.

  1. Article
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  6. Pathogenesis of Zika Virus Infection.Annual review of pathology · 2023
    Review
  7. Article
  8. Review
  9. Article
  10. Dengue virus NS4B protein as a target for developing antivirals.Frontiers in cellular and infection microbiology · 2022
    Review
  11. Review
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  13. Article
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  15. Article
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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 3 institutions in 2 countries.

Maria Isabel GiraldoCentro de Investigaciones Biomédicas, Universidad del Quindío, Cra 15 Cl 12N, Armenia, Colombia; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA. Electronic address: migirald@utmb.edu.
Oscar Vargas-CuartasCentro de Investigaciones Biomédicas, Universidad del Quindío, Cra 15 Cl 12N, Armenia, Colombia. Electronic address: ovargascuartas@gmail.com.
Juan Carlos Gallego-GomezGrupo de Medicina Molecular y de Traslación, Universidad de Antioquia, Cra. 51 D No. 62-29, Medellin, Colombia. Electronic address: carlos.gallego@udea.edu.co.
Pei-Yong ShiDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA. Electronic address: peshi@utmb.edu.
Leonardo Padilla-SanabriaCentro de Investigaciones Biomédicas, Universidad del Quindío, Cra 15 Cl 12N, Armenia, Colombia. Electronic address: lpadilla@uniquindio.edu.co.
Jhon Carlos Castaño-OsorioCentro de Investigaciones Biomédicas, Universidad del Quindío, Cra 15 Cl 12N, Armenia, Colombia. Electronic address: jhoncarlos@uniquindio.edu.co.
Ricardo RajsbaumDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA. Electronic address: rirajsba@utmb.edu.
University of Quindío · COThe University of Texas Medical Branch at Galveston · USUniversidad de Antioquia · CO

Funding

UTMB WOMEN'S HEALTH RESEARCH SCHOLARS PROGRAMK12HD052023 · NICHD · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI BERENSON, ABBEY B · 2005 to 2023
$8.1M
Unanchored Polyubiquitin Chains and Innate Immunity to Influenza VirusR21AI126012 · NIAID · UNIVERSITY OF TEXAS MED BR GALVESTON · PI RAJSBAUM, RICARDO · 2017 to 2018
$426k
The role of the host ubiquitin system in Zika virus replicationR21AI132479 · NIAID · UNIVERSITY OF TEXAS MED BR GALVESTON · PI RAJSBAUM, RICARDO · 2017 to 2018
$426k
NIAID NIH HHS R21 AI126012NIAID NIH HHS R21 AI132479NICHD NIH HHS K12 HD052023
6 · The paper itself

Abstract

Dengue virus (DENV) is a member of the Flaviviridae family, which is transmitted to mammalian species through arthropods, and causes dengue fever or severe dengue fever in humans. The DENV genome encodes for multiple nonstructural (NS) proteins including NS1. NS1 plays an essential role in replication by interacting with other viral proteins including NS4B, however how these interactions are regulated during virus infection is not known. By using bioinformatics, mass spectrometry analysis, and co-immunoprecipitation assays, here we show that DENV-NS1 is ubiquitinated on multiples lysine residues during DENV infection, including K189, a lysine residue previously shown to be important for efficient DENV replication. Data from in vitro and cell culture experiments indicate that dengue NS1 undergoes modification with K48-linked polyubiquitin chains, which usually target proteins to the proteasome for degradation. Furthermore, ubiquitinated NS1 was detected in lysates as well as in supernatants of human and mosquito infected cells. Ubiquitin deconjugation of NS1 using the deubiquitinase OTU resulted in increased interaction with the viral protein NS4B suggesting that ubiquitinated NS1 has reduced affinity for NS4B. In support of these data, a K189R mutation on NS1, which abrogates ubiquitination on amino acid residue 189 of NS1, also increased NS1-NS4B interactions. Our work describes a new mechanism of regulation of NS1-NS4B interactions and suggests that ubiquitination of NS1 may affect DENV replication.

Indexed as

Gene Expression Regulation, ViralVirus ReplicationAmino Acid SequenceAnimalsCell Line, TumorComputational BiologyCulicidaeDengue VirusHEK293 CellsHepatocytesHumansLysineMutationProteasome Endopeptidase ComplexProtein BindingProteolysisLysineNS1 protein, Dengue virus type 2NS4B protein, flavivirusOTUD1 protein, humanProteasome Endopeptidase ComplexRecombinant ProteinsUbiquitin-Specific ProteasesViral Nonstructural ProteinsDengue virusDeubiquitinaseK48-linked polyubiquitinNS1NS4BProteasomeUbiquitination

Identifiers

PMID29294313
PMCPMC5811335
OpenAlexW2776271502

What OpenQuestion holds

Textmetadata
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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.