Evidence map›Paper›PMID 29070688›Full record

ArticleJournal of virology2018

Structural Basis for Escape of Human Astrovirus from Antibody Neutralization: Broad Implications for Rational Vaccine Design.

Walter A Bogdanoff, Edmundo I Perez, Tomás López, Carlos F Arias, Rebecca M DuBois

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

22 citing papers in PubMed, 33 citations in OpenAlex.

  1. Designing a novel and effective multi-epitope subunit vaccine against human astrovirus using reverse vaccinology approach.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2026
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  11. Structure of the divergent human astrovirus MLB capsid spike.Structure (London, England : 1993) · 2022
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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

5 authors at 2 institutions in 2 countries.

Walter A BogdanoffDepartment of Biomolecular Engineering, University of California-Santa Cruz, Santa Cruz, California, USA.ORCID http://orcid.org/0000-0001-6532-1006
Edmundo I PerezDepartment of Biomolecular Engineering, University of California-Santa Cruz, Santa Cruz, California, USA.
Tomás LópezDepartamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico.
Carlos F AriasDepartamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, Mexico.ORCID http://orcid.org/0000-0003-3130-4501
Rebecca M DuBoisDepartment of Biomolecular Engineering, University of California-Santa Cruz, Santa Cruz, California, USA rmdubois@ucsc.edu.
University of California, Santa Cruz · USUniversidad Nacional Autónoma de México · MX

Funding

UNIVERSITY OF CALIFORNIA, SANTA CRUZ IMSD PROGRAMR25GM058903 · NIGMS · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI JURICA, MELISSA S · 1999 to 2019
$12.2M
Training Program/Molecular/Cell/Developmental BiologyT32GM008646 · NIGMS · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI STROME, SUSAN · 1999 to 2018
$3.7M
Structural and mechanistic insights into antibody neutralization of human astrovirusR56AI130073 · NIAID · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI DUBOIS, REBECCA MICHELLE · 2017 to 2017
$303k
Crystal structures and mechanism of disease of the astrovirus capsid proteinK22AI095369 · NIAID · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI DUBOIS, REBECCA MICHELLE · 2013 to 2014
$264k
NIAID NIH HHS K22 AI095369NIAID NIH HHS R56 AI130073NIGMS NIH HHS R25 GM058903NIGMS NIH HHS T32 GM008646
6 · The paper itself

Abstract

Human astroviruses are recognized as a leading cause of viral diarrhea worldwide in children, immunocompromised patients, and the elderly. There are currently no vaccines available to prevent astrovirus infection; however, antibodies developed by healthy individuals during previous infection correlate with protection from reinfection, suggesting that an effective vaccine could be developed. In this study, we investigated the molecular mechanism by which several strains of human astrovirus serotype 2 (HAstV-2) are resistant to the potent HAstV-2-neutralizing monoclonal antibody PL-2 (MAb PL-2). Sequencing of the HAstV-2 capsid genes reveals mutations in the PL-2 epitope within the capsid's spike domain. To understand the molecular basis for resistance from MAb PL-2 neutralization, we determined the 1.35-Å-resolution crystal structure of the capsid spike from one of these HAstV-2 strains. Our structure reveals a dramatic conformational change in a loop within the PL-2 epitope due to a serine-to-proline mutation, locking the loop in a conformation that sterically blocks binding and neutralization by MAb PL-2. We show that mutation to serine permits loop flexibility and recovers MAb PL-2 binding. Importantly, we find that HAstV-2 capsid spike containing a serine in this loop is immunogenic and elicits antibodies that neutralize all HAstV-2 strains. Taken together, our results have broad implications for rational selection of vaccine strains that do not contain prolines in antigenic loops, so as to elicit antibodies against diverse loop conformations.

Indexed as

Antibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralCapsidCapsid ProteinsDrug DesignEpitopesHumansMamastrovirusModels, MolecularMolecular ConformationMutationProlineProtein BindingSequence Analysis, DNASerineAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralCapsid ProteinsEpitopesProlineSerineViral Vaccinesastrovirusneutralizing antibodiesstructure-activity relationshipsvaccines

Identifiers

PMID29070688
PMCPMC5730766
OpenAlexW2766634477

What OpenQuestion holds

Textmetadata
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.