Evidence map›Paper›PMID 31415678›Full record

ArticlePLoS pathogens2019

Dysregulation of M segment gene expression contributes to influenza A virus host restriction.

Brenda M Calderon, Shamika Danzy, Gabrielle K Delima, Nathan T Jacobs, Ketaki Ganti, Megan R Hockman, Graeme L Conn, Anice C Lowen, John Steel

Abstract read
In one paragraph

Article in PLoS pathogens, 2019. 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
–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

22 citing papers in PubMed.

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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

9 authors.

Brenda M CalderonDepartment of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, United States of America.ORCID 0000-0003-1130-0386
Shamika DanzyDepartment of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, United States of America.ORCID 0000-0002-7261-4146
Gabrielle K DelimaDepartment of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, United States of America.ORCID 0000-0003-4593-7924
Nathan T JacobsDepartment of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, United States of America.ORCID 0000-0003-3026-670X
Ketaki GantiDepartment of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, United States of America.ORCID 0000-0002-9687-3505
Megan R HockmanDepartment of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, United States of America.ORCID 0000-0002-1818-1079
Graeme L ConnDepartment of Biochemistry, Emory University School of Medicine, Atlanta, GA, United States of America.ORCID 0000-0002-2419-380X
Anice C LowenDepartment of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, United States of America.ORCID 0000-0002-9829-112X
John SteelDepartment of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, United States of America.ORCID 0000-0003-1217-0990

Funding

NIAID NIH HHS HHSN272201400004C
6 · The paper itself

Abstract

The M segment of the 2009 pandemic influenza A virus (IAV) has been implicated in its emergence into human populations. To elucidate the genetic contributions of the M segment to host adaptation, and the underlying mechanisms, we examined a panel of isogenic viruses that carry avian- or human-derived M segments. Avian, but not human, M segments restricted viral growth and transmission in mammalian model systems, and the restricted growth correlated with increased expression of M2 relative to M1. M2 overexpression was associated with intracellular accumulation of autophagosomes, which was alleviated by interference of the viral proton channel activity by amantadine treatment. As M1 and M2 are expressed from the M mRNA through alternative splicing, we separated synonymous and non-synonymous changes that differentiate human and avian M segments and found that dysregulation of gene expression leading to M2 overexpression diminished replication, irrespective of amino acid composition of M1 or M2. Moreover, in spite of efficient replication, virus possessing a human M segment that expressed avian M2 protein at low level did not transmit efficiently. We conclude that (i) determinants of transmission reside in the IAV M2 protein, and that (ii) control of M segment gene expression is a critical aspect of IAV host adaptation needed to prevent M2-mediated dysregulation of vesicular homeostasis.

Indexed as

Virus ReplicationA549 CellsAnimalsBirdsDogsFemaleGuinea PigsHumansInfluenza A virusInfluenza, HumanMadin Darby Canine Kidney CellsOrthomyxoviridae InfectionsSpecies SpecificityViral Matrix ProteinsViroporin ProteinsM2 protein, Influenza A virusViral Matrix ProteinsViroporin Proteins

Identifiers

PMID31415678
PMCPMC6695095

What OpenQuestion holds

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LicenceCC BY
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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.