Evidence map›Paper›PMID 31019050›Full record

ArticleJournal of virology2019

Deep Mutational Scan of the Highly Conserved Influenza A Virus M1 Matrix Protein Reveals Substantial Intrinsic Mutational Tolerance.

Nancy Hom, Lauren Gentles, Jesse D Bloom, Kelly K Lee

Abstract read
In one paragraph

Article in Journal of virology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing 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

31 citing papers in PubMed.

  1. Review
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  14. popDMS infers mutation effects from deep mutational scanning data.bioRxiv : the preprint server for biology · 2024
    Article
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  20. Exploring the expanse between theoretical questions and experimental approaches in the modern study of evolvability.Journal of experimental zoology. Part B, Molecular and developmental evolution · 2023
    Article
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

4 authors.

Nancy HomDepartment of Medicinal Chemistry, University of Washington, Seattle, Washington, USA.
Lauren GentlesDepartment of Microbiology, University of Washington, Seattle, Washington, USA.
Jesse D BloomDepartment of Microbiology, University of Washington, Seattle, Washington, USA.ORCID 0000-0003-1267-3408
Kelly K LeeDepartment of Medicinal Chemistry, University of Washington, Seattle, Washington, USA kklee@uw.edu.

Funding

Structural and dynamic traits underlying phenotypic variation in HIV-1 EnvR01AI140868 · NIAID · UNIVERSITY OF WASHINGTON · PI Kelly Keisen Lee · 2019 to 2026
$5.3M
Waters ACQUITY UPLC M-Class with NanoLockSpray ionization sourceR01GM099989 · NIGMS · UNIVERSITY OF WASHINGTON · PI LEE, KELLY KEISEN · 2012 to 2020
$3.5M
High-throughput experiments to guide influenza vaccine strain selectionR01AI127893 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI BLOOM, JESSE D · 2016 to 2020
$2.1M
FHCRC High-Performance Computing ClusterS10OD020069 · OD · FRED HUTCHINSON CANCER RESEARCH CENTER · PI KOOPERBERG, CHARLES L · 2015 to 2015
$600k
Howard Hughes Medical InstituteNIAID NIH HHS R01 AI127893NIGMS NIH HHS R01 GM099989NIH HHS S10 OD020069
6 · The paper itself

Abstract

Influenza A virus matrix protein M1 is involved in multiple stages of the viral infectious cycle. Despite its functional importance, our present understanding of this essential viral protein is limited. The roles of a small subset of specific amino acids have been reported, but a more comprehensive understanding of the relationship between M1 sequence, structure, and virus fitness remains elusive. In this study, we used deep mutational scanning to measure the effect of every amino acid substitution in M1 on viral replication in cell culture. The map of amino acid mutational tolerance we have generated allows us to identify sites that are functionally constrained in cell culture as well as sites that are less constrained. Several sites that exhibit low tolerance to mutation have been found to be critical for M1 function and production of viable virions. Surprisingly, significant portions of the M1 sequence, especially in the C-terminal domain, whose structure is undetermined, were found to be highly tolerant of amino acid variation, despite having extremely low levels of sequence diversity among natural influenza virus strains. This unexpected discrepancy indicates that not all sites in M1 that exhibit high sequence conservation in nature are under strong constraint during selection for viral replication in cell culture.

Indexed as

Conserved SequenceMutationAmino Acid SequenceAmino Acid SubstitutionCell LineEvolution, MolecularHEK293 CellsHumansInfluenza A virusInfluenza, HumanModels, MolecularProtein ConformationProtein DomainsViral Matrix ProteinsVirionVirus AssemblyM1 protein, Influenza A virusViral Matrix Proteinscodon librarydeep mutational scaninfluenza A virusM1 matrixmutational toleranceselectionviral evolution

Identifiers

PMID31019050
PMCPMC6580950

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.