Evidence map›Paper›PMID 28674411›Full record

ArticleScientific reports2017

In Vitro Assembly and Stabilization of Dengue and Zika Virus Envelope Protein Homo-Dimers.

Stefan W Metz, Emily N Gallichotte, Alex Brackbill, Lakshmanane Premkumar, Michael J Miley, Ralph Baric, Aravinda M de Silva

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
7.2field-weighted citation impact, top 3% 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

28 citing papers in PubMed, 47 citations in OpenAlex.

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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 1 institution in 1 country.

Stefan W MetzDepartment of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA. swmetz@med.unc.edu.
Emily N GallichotteDepartment of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Alex BrackbillDepartment of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Lakshmanane PremkumarDepartment of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Michael J MileyDepartment of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Ralph BaricDepartment of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Aravinda M de SilvaDepartment of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA. aravinda_desilva@med.unc.edu.
University of North Carolina at Chapel Hill · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
Protein Expression/Dengue Virology CoreU19AI109784 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI TING, JENNY P · 2014 to 2018
$20.8M
Molecular Basis of Flavivirus Cross-Neutralization by Human AntibodiesR01AI107731 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DESILVA, ARAVINDA M. · 2013 to 2022
$5.3M
NIAID NIH HHS R01 AI107731NIAID NIH HHS U19 AI109784
6 · The paper itself

Abstract

Zika virus (ZIKV) and the 4 dengue virus (DENV) serotypes are mosquito-borne Flaviviruses that are associated with severe neuronal and hemorrhagic syndromes. The mature flavivirus infectious virion has 90 envelope (E) protein homo-dimers that pack tightly to form a smooth protein coat with icosahedral symmetry. Human antibodies that strongly neutralize ZIKV and DENVs recognize complex quaternary structure epitopes displayed on E-homo-dimers and higher order structures. The ZIKV and DENV E protein expressed as a soluble protein is mainly a monomer that does not display quaternary epitopes, which may explain the modest success with soluble recombinant E (sRecE) as a vaccine and diagnostic antigen. New strategies are needed to design recombinant immunogens that display these critical immune targets. Here we present two novel methods for building or stabilizing in vitro E-protein homo-dimers that display quaternary epitopes. In the first approach we immobilize sRecE to enable subsequent dimer generation. As an alternate method, we describe the use of human mAbs to stabilize homo-dimers in solution. The ability to produce recombinant E protein dimers displaying quaternary structure epitopes is an important advance with applications in flavivirus diagnostics and vaccine development.

Indexed as

Dengue VirusProtein MultimerizationVirus AssemblyZika VirusAnimalsAntibodies, ViralBinding SitesCells, CulturedEpitopesHumansNeutralization TestsProtein BindingProtein Interaction Domains and MotifsProtein StabilityRecombinant ProteinsSerogroupAntibodies, ViralEpitopesRecombinant ProteinsViral Envelope Proteins

Identifiers

PMID28674411
PMCPMC5495877
OpenAlexW2724475480

What OpenQuestion holds

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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.