Evidence map›Paper›PMID 39013466›Full record

ArticleImmunity2024

Deep mutational scanning reveals functional constraints and antibody-escape potential of Lassa virus glycoprotein complex.

Caleb R Carr, Katharine H D Crawford, Michael Murphy, Jared G Galloway, Hugh K Haddox, Frederick A Matsen, Kristian G Andersen, Neil P King, Jesse D Bloom

Abstract read
In one paragraph

Article in Immunity, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
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

18 citing papers in PubMed.

  1. Article
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  3. Functional dissection ofProceedings of the National Academy of Sciences of the United States of America · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Caleb R CarrBasic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Medical Scientist Training Program, University of Washington, Seattle, WA 98195, USA.
Katharine H D CrawfordBasic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Medical Scientist Training Program, University of Washington, Seattle, WA 98195, USA.
Michael MurphyDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Jared G GallowayBasic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Hugh K HaddoxBasic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Frederick A MatsenBasic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA; Department of Statistics, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, Seattle, WA 98109, USA.
Kristian G AndersenDepartment of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Scripps Research Translational Institute, La Jolla, CA 92037, USA.
Neil P KingDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Jesse D BloomBasic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, Seattle, WA 98109, USA. Electronic address: jbloom@fredhutch.org.

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Eric Collisson · 1985 to 2026
$296.4M
Technology CoreU19AI135995 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI Kristian Graugaard Andersen · 2018 to 2026
$32.0M
Scripps Translational Science InstituteUL1TR002550 · NCATS · SCRIPPS RESEARCH INSTITUTE, THE · PI TOPOL, ERIC JEFFREY · 2018 to 2022
$28.9M
West African Emerging Infectious Disease Research Center (WA-EIDRC)U01AI151812 · NIAID · SCRIPPS RESEARCH INSTITUTE, THE · PI ANDERSEN, KRISTIAN GRAUGAARD, GARRY, ROBERT F · 2020 to 2024
$13.2M
Prospectively characterizing the functional and antigenic effects of mutations to viral entry proteinsR01AI141707 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BLOOM, JESSE D · 2018 to 2022
$2.1M
High-Performance Compute Cluster for Comprehensive Cancer and Infectious Diseases ResearchS10OD028685 · OD · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BRADLEY, PHILIP · 2020 to 2020
$2.0M
FHCRC High-Performance Computing ClusterS10OD020069 · OD · FRED HUTCHINSON CANCER RESEARCH CENTER · PI KOOPERBERG, CHARLES L · 2015 to 2015
$600k
Complete mapping of the functional and antigenic effects of mutations to Lassa virus glycoproteinF30AI149928 · NIAID · UNIVERSITY OF WASHINGTON · PI CRAWFORD, KATHARINE HOLT DUSENBURY · 2020 to 2021
$91k
Howard Hughes Medical InstituteNCATS NIH HHS UL1 TR002550NCI NIH HHS P30 CA015704NIAID NIH HHS F30 AI149928NIAID NIH HHS R01 AI141707NIAID NIH HHS U01 AI151812NIAID NIH HHS U19 AI135995NIH HHS S10 OD020069NIH HHS S10 OD028685
6 · The paper itself

Abstract

Lassa virus is estimated to cause thousands of human deaths per year, primarily due to spillovers from its natural host, Mastomys rodents. Efforts to create vaccines and antibody therapeutics must account for the evolutionary variability of the Lassa virus's glycoprotein complex (GPC), which mediates viral entry into cells and is the target of neutralizing antibodies. To map the evolutionary space accessible to GPC, we used pseudovirus deep mutational scanning to measure how nearly all GPC amino-acid mutations affected cell entry and antibody neutralization. Our experiments defined functional constraints throughout GPC. We quantified how GPC mutations affected neutralization with a panel of monoclonal antibodies. All antibodies tested were escaped by mutations that existed among natural Lassa virus lineages. Overall, our work describes a biosafety-level-2 method to elucidate the mutational space accessible to GPC and shows how prospective characterization of antigenic variation could aid the design of therapeutics and vaccines.

Indexed as

Antibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralLassa FeverLassa virusMutationAnimalsGlycoproteinsHEK293 CellsHumansImmune EvasionViral Envelope ProteinsVirus InternalizationAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralGlycoproteinsViral Envelope Proteinsantibody escapeantigenic variationarena virusArevirumabArevirumab-3deep mutational scanningglobal epistasisGPCLassa virus

Identifiers

PMID39013466
PMCPMC11390330

What OpenQuestion holds

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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.