Evidence map›Paper›PMID 29258238›Full record

ArticleViruses2017

Stress Granule-Inducing Eukaryotic Translation Initiation Factor 4A Inhibitors Block Influenza A Virus Replication.

Patrick D Slaine, Mariel Kleer, Nathan K Smith, Denys A Khaperskyy, Craig McCormick

Open access · goldAbstract read
In one paragraph

Article in Viruses, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
7.6field-weighted citation impact, top 4% 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

35 citing papers in PubMed, 54 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

5 authors at 1 institution in 1 country.

Patrick D SlaineDepartment of Microbiology and Immunology, Dalhousie University, 5850 College Street, Halifax, NS B3H 4R2, Canada. patrick.slaine@dal.ca.
Mariel KleerDepartment of Microbiology and Immunology, Dalhousie University, 5850 College Street, Halifax, NS B3H 4R2, Canada. mariel.kleer@dal.ca.
Nathan K SmithDepartment of Community Health and Epidemiology, Dalhousie University, 5790 University Avenue, Halifax, NS B3H 1V7, Canada. nathansmith@dal.ca.
Denys A KhaperskyyDepartment of Microbiology and Immunology, Dalhousie University, 5850 College Street, Halifax, NS B3H 4R2, Canada. d.khaperskyy@dal.ca.
Craig McCormickDepartment of Microbiology and Immunology, Dalhousie University, 5850 College Street, Halifax, NS B3H 4R2, Canada. craig.mccormick@dal.ca.ORCID 0000-0003-2794-3722
Dalhousie University · CA

Funding

CIHR MOP-136817CIHR PJT 148727
6 · The paper itself

Abstract

Eukaryotic translation initiation factor 4A (eIF4A) is a helicase that facilitates assembly of the translation preinitiation complex by unwinding structured mRNA 5' untranslated regions. Pateamine A (PatA) and silvestrol are natural products that disrupt eIF4A function and arrest translation, thereby triggering the formation of cytoplasmic aggregates of stalled preinitiation complexes known as stress granules (SGs). Here we examined the effects of eIF4A inhibition by PatA and silvestrol on influenza A virus (IAV) protein synthesis and replication in cell culture. Treatment of infected cells with either PatA or silvestrol at early times post-infection resulted in SG formation, arrest of viral protein synthesis and failure to replicate the viral genome. PatA, which irreversibly binds to eIF4A, sustained long-term blockade of IAV replication following drug withdrawal, and inhibited IAV replication at concentrations that had minimal cytotoxicity. By contrast, the antiviral effects of silvestrol were fully reversible; drug withdrawal caused rapid SG dissolution and resumption of viral protein synthesis. IAV inhibition by silvestrol was invariably associated with cytotoxicity. PatA blocked replication of genetically divergent IAV strains, suggesting common dependence on host eIF4A activity. This study demonstrates that the core host protein synthesis machinery can be targeted to block viral replication.

Indexed as

A549 CellsAntiviral AgentsBenzofuransEnzyme InhibitorsEpoxy CompoundsEukaryotic Initiation Factor-4AHumansInfluenza A virusMacrolidesProtein BiosynthesisThiazolesTriterpenesVirus ReplicationAntiviral AgentsBenzofuransEnzyme InhibitorsEpoxy CompoundsEukaryotic Initiation Factor-4AMacrolidespateamine AsilvestrolThiazolesTriterpeneseIF4A helicaseinfluenza A viruspateamine Asilvestrolstress granuletranslation

Identifiers

PMID29258238
PMCPMC5744162
OpenAlexW2758094822

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.