Evidence map›Paper›PMID 31662457›Full record

ArticlemBio2019

Zika Virus NS2A-Mediated Virion Assembly.

Xianwen Zhang, Xuping Xie, Hongjie Xia, Jing Zou, Linfen Huang, Vsevolod L Popov, Xinwen Chen, Pei-Yong Shi

Open access · goldAbstract read
In one paragraph

Article in mBio, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
9.5field-weighted citation impact, top 2% 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

66 citing papers in PubMed, 86 citations in OpenAlex.

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6 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

8 authors at 2 institutions in 2 countries.

Xianwen ZhangDepartment of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA.
Xuping XieDepartment of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA xuxie@utmb.edu chenxw@wh.iov.cn peshi@utmb.edu.ORCID 0000-0003-0918-016X
Hongjie XiaDepartment of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA.
Jing ZouDepartment of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA.
Linfen HuangDepartment of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA.
Vsevolod L PopovDepartment of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
Xinwen ChenState Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, People's Republic of China xuxie@utmb.edu chenxw@wh.iov.cn peshi@utmb.edu.
Pei-Yong ShiDepartment of Biochemistry & Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA xuxie@utmb.edu chenxw@wh.iov.cn peshi@utmb.edu.
The University of Texas Medical Branch at Galveston · USChinese Academy of Sciences · CN

Funding

Project 4 - Influenza - UABU19AI142759 · NIAID · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BOSTWICK, JAMES ROBERT · 2019 to 2023
$37.5M
Revolutionary Eilat-based Chikungunya Vaccine VectorR01AI127744 · NIAID · UNIVERSITY OF TEXAS MED BR GALVESTON · PI WANG, TIAN · 2017 to 2021
$3.5M
Discovery of Zika virus therapeutics using a replicon assayR41AI136126 · NIAID · MICROBIOTIX, INC · PI BOWLIN, TERRY L. · 2018 to 2019
$585k
NIAID NIH HHS R01 AI127744NIAID NIH HHS R41 AI136126NIAID NIH HHS U19 AI142759
6 · The paper itself

Abstract

The flavivirus virion consists of an envelope outer layer, formed by envelope (E) and membrane (M) proteins on a lipid bilayer, and an internal core, formed by capsid (C) protein and genomic RNA. The molecular mechanism of flavivirus assembly is not well understood. Here, we show that Zika virus (ZIKV) NS2A protein recruits genomic RNA, the structural protein prM/E complex, and the NS2B/NS3 protease complex to the virion assembly site and orchestrates virus morphogenesis. Coimmunoprecipitation analysis showed that ZIKV NS2A binds to prM, E, NS2B, and NS3 (but not C, NS4B, or NS5) in a viral RNA-independent manner, whereas prM/E complex does not interact with NS2B/NS3 complex. Remarkably, a single-amino-acid mutation (E103A) of NS2A impairs its binding to prM/E and NS2B/NS3 and abolishes virus production, demonstrating the indispensable role of NS2A/prM/E and NS2A/NS2B/NS3 interactions in virion assembly. In addition, RNA-protein pulldown analysis identified a stem-loop RNA from the 3' untranslated region (UTR) of the viral genome as an "RNA recruitment signal" for ZIKV assembly. The 3' UTR RNA binds to a cytoplasmic loop of NS2A protein. Mutations of two positively charged residues (R96A and R102A) from the cytoplasmic loop reduce NS2A binding to viral RNA, leading to a complete loss of virion assembly. Collectively, our results support a virion assembly model in which NS2A recruits viral NS2B/NS3 protease and structural C-prM-E polyprotein to the virion assembly site; once the C-prM-E polyprotein has been processed, NS2A presents viral RNA to the structural proteins for virion assembly.

Indexed as

DEAD-box RNA HelicasesFemaleFlavivirusGenome, ViralHumansMutationNucleocapsidNucleoside-TriphosphatasePeptide HydrolasesPregnancyRNA, ViralSerine EndopeptidasesViral Envelope ProteinsViral Nonstructural ProteinsViral ProteasesViral ProteinsDEAD-box RNA HelicasesNS2B protein, flavivirusNS3 protein, Zika virusNucleoside-TriphosphatasePeptide HydrolasesprM protein, FlavivirusRNA, ViralSerine EndopeptidasesViral Envelope ProteinsViral Nonstructural ProteinsViral ProteasesViral Proteinsflavivirusvirus assemblyZika

Identifiers

PMID31662457
PMCPMC6819661
OpenAlexW2982308767

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.