Evidence map›Paper›PMID 29702546›Full record

ArticleViruses2018

Mutation of CD2AP and SH3KBP1 Binding Motif in Alphavirus nsP3 Hypervariable Domain Results in Attenuated Virus.

Margit Mutso, Ainhoa Moliner Morro, Cecilia Smedberg, Sergo Kasvandik, Muriel Aquilimeba, Mona Teppor, Liisi Tarve, Aleksei Lulla, Valeria Lulla, Sirle Saul and 4 more

Open access · goldAbstract read
In one paragraph

Article in Viruses, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
7.4field-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

36 citing papers in PubMed, 51 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

14 authors at 2 institutions in 2 countries.

Margit MutsoInstitute of Technology, University of Tartu, 50411 Tartu, Estonia. m.mutso@griffith.edu.au.
Ainhoa Moliner MorroDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden. ainhoa.moliner.morro@ki.se.
Cecilia SmedbergDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden. Cecilia.Smedberg@ki.se.
Sergo KasvandikInstitute of Technology, University of Tartu, 50411 Tartu, Estonia. sergo.kasvandik@ut.ee.ORCID 0000-0003-0218-2410
Muriel AquilimebaInstitute of Technology, University of Tartu, 50411 Tartu, Estonia. muriel.aquilimeba@hotmail.fr.
Mona TepporInstitute of Technology, University of Tartu, 50411 Tartu, Estonia. mona.teppor@ut.ee.
Liisi TarveInstitute of Technology, University of Tartu, 50411 Tartu, Estonia. tarve.liisi@gmail.com.
Aleksei LullaInstitute of Technology, University of Tartu, 50411 Tartu, Estonia. aleksei.lulla@gmail.com.
Valeria LullaInstitute of Technology, University of Tartu, 50411 Tartu, Estonia. leralulla@gmail.com.
Sirle SaulInstitute of Technology, University of Tartu, 50411 Tartu, Estonia. sirlesaul@gmail.com.
Bastian ThaaDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden. bthaa@gmx.de.ORCID 0000-0001-8800-9584
Gerald M McInerneyDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden. Gerald.McInerney@ki.se.ORCID 0000-0003-2257-7241
Andres MeritsInstitute of Technology, University of Tartu, 50411 Tartu, Estonia. andres.merits@ut.ee.
Margus VarjakInstitute of Technology, University of Tartu, 50411 Tartu, Estonia. margus.varjak@glasgow.ac.uk.ORCID 0000-0003-2608-5148
University of Tartu · EEKarolinska Institutet · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Infection by Chikungunya virus (CHIKV) of the Old World alphaviruses (family Togaviridae) in humans can cause arthritis and arthralgia. The virus encodes four non-structural proteins (nsP) (nsP1, nsp2, nsP3 and nsP4) that act as subunits of the virus replicase. These proteins also interact with numerous host proteins and some crucial interactions are mediated by the unstructured C-terminal hypervariable domain (HVD) of nsP3. In this study, a human cell line expressing EGFP tagged with CHIKV nsP3 HVD was established. Using quantitative proteomics, it was found that CHIKV nsP3 HVD can bind cytoskeletal proteins, including CD2AP, SH3KBP1, CAPZA1, CAPZA2 and CAPZB. The interaction with CD2AP was found to be most evident; its binding site was mapped to the second SH3 ligand-like element in nsP3 HVD. Further assessment indicated that CD2AP can bind to nsP3 HVDs of many different New and Old World alphaviruses. Mutation of the short binding element hampered the ability of the virus to establish infection. The mutation also abolished ability of CD2AP to co-localise with nsP3 and replication complexes of CHIKV; the same was observed for Semliki Forest virus (SFV) harbouring a similar mutation. Similar to CD2AP, its homolog SH3KBP1 also bound the identified motif in CHIKV and SFV nsP3.

Indexed as

Adaptor Proteins, Signal TransducingAlphavirusAmino Acid MotifsAnimalsBinding SitesCapZ Actin Capping ProteinCell LineChikungunya virusCricetinaeCytoskeletal ProteinsHost-Pathogen InteractionsHumansMutationProtein BindingSemliki forest virusViral Nonstructural ProteinsAdaptor Proteins, Signal TransducingCapZ Actin Capping ProteinCD2-associated proteinCytoskeletal ProteinsSH3KBP1 protein, humanViral Nonstructural ProteinsalphavirusCD2APChikungunya virusproteomicsSH3KBP1SH3 ligand

Identifiers

PMID29702546
PMCPMC5977219
OpenAlexW2802649881

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.