Evidence map›Paper›PMID 25326389›Full record

ArticleThe Journal of biological chemistry2014

Highly conserved residues in the helical domain of dengue virus type 1 precursor membrane protein are involved in assembly, precursor membrane (prM) protein cleavage, and entry.

Szu-Chia Hsieh, Yi-Chieh Wu, Gang Zou, Vivek R Nerurkar, Pei-Yong Shi, Wei-Kung Wang

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 10% 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

34 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.

  1. Pooled it
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  15. Seeking heterocyclic scaffolds as antivirals against dengue virus.European journal of medicinal chemistry · 2022
    Review
  16. Article
  17. Article
  18. Microbiology spectrum · 2021
    Article
  19. Article
  20. 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.

Szu-Chia HsiehFrom the Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii 96813 and.
Yi-Chieh WuFrom the Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii 96813 and.
Gang Zouthe Wadsworth Center, New York State Department of Health, Albany, New York 12208.
Vivek R NerurkarFrom the Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii 96813 and.
Pei-Yong Shithe Wadsworth Center, New York State Department of Health, Albany, New York 12208.
Wei-Kung WangFrom the Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii 96813 and wangwk@hawaii.edu.
University of Hawaiʻi at Mānoa · US

Funding

Pacific Center for Emerging Infectious Diseases ResearchP20GM103516 · NIGMS · UNIVERSITY OF HAWAII AT MANOA · PI YANAGIHARA, RICHARD · 2012 to 2014
$6.1M
NIGMS NIH HHS P20 GM103516NIGMS NIH HHS P20GM103516
6 · The paper itself

Abstract

The envelope and precursor membrane (prM) proteins of dengue virus (DENV) are present on the surface of immature virions. During maturation, prM protein is cleaved by furin protease into pr peptide and membrane (M) protein. Although previous studies mainly focusing on the pr region have identified several residues important for DENV replication, the functional role of M protein, particularly the α-helical domain (MH), which is predicted to undergo a large conformational change during maturation, remains largely unknown. In this study, we investigated the role of nine highly conserved MH domain residues in the replication cycle of DENV by site-directed mutagenesis in a DENV1 prME expression construct and found that alanine substitutions introduced to four highly conserved residues at the C terminus and one at the N terminus of the MH domain greatly affect the production of both virus-like particles and replicon particles. Eight of the nine alanine mutants affected the entry of replicon particles, which correlated with the impairment in prM cleavage. Moreover, seven mutants were found to have reduced prM-E interaction at low pH, which may inhibit the formation of smooth immature particles and exposure of prM cleavage site during maturation, thus contributing to inefficient prM cleavage. Taken together, these results are the first report showing that highly conserved MH domain residues, located at 20-38 amino acids downstream from the prM cleavage site, can modulate the prM cleavage, maturation of particles, and virus entry. The highly conserved nature of these residues suggests potential targets of antiviral strategy.

Indexed as

ProteolysisVirus InternalizationAmino Acid SubstitutionCell LineDengue VirusHumansMutagenesis, Site-DirectedMutation, MissenseProtein Structure, TertiaryViral Matrix ProteinsVirus ReplicationViral Matrix ProteinsDengue VirusFlavivirusMaturationMembrane ProteinPlus-stranded RNA VirusReplicon ParticlesVirus AssemblyVirus Structure

Identifiers

PMID25326389
PMCPMC4246076
OpenAlexW2025988707

What OpenQuestion holds

Textmetadata
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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.