Evidence map›Paper›PMID 28228588›Full record

ArticleJournal of virology2017

Investigation of the Role of Protein Kinase D in Human Rhinovirus Replication.

Anabel Guedán, Dawid Swieboda, Mark Charles, Marie Toussaint, Sebastian L Johnston, Amin Asfor, Anusha Panjwani, Tobias J Tuthill, Henry Danahay, Tony Raynham and 2 more

Open access · hybridAbstract read
In one paragraph

Article in Journal of virology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.4field-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

21 citing papers in PubMed, 29 citations in OpenAlex.

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  7. Protein kinase D1 - A targetable mediator of pancreatic cancer development.Biochimica et biophysica acta. Molecular cell research · 2024
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  10. HAP1, a new revolutionary cell model for gene editing using CRISPR-Cas9.Frontiers in cell and developmental biology · 2023
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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

12 authors at 4 institutions in 1 country.

Anabel GuedánNational Heart and Lung Institute, Imperial College of Science, Technology and Medicine, London, United Kingdom.
Dawid SwiebodaNational Heart and Lung Institute, Imperial College of Science, Technology and Medicine, London, United Kingdom.
Mark CharlesCRT Discovery Laboratories, Cambridge, United Kingdom.
Marie ToussaintNational Heart and Lung Institute, Imperial College of Science, Technology and Medicine, London, United Kingdom.
Sebastian L JohnstonNational Heart and Lung Institute, Imperial College of Science, Technology and Medicine, London, United Kingdom.
Amin AsforThe Pirbright Institute, Pirbright, Surrey, United Kingdom.
Anusha PanjwaniThe Pirbright Institute, Pirbright, Surrey, United Kingdom.
Tobias J TuthillThe Pirbright Institute, Pirbright, Surrey, United Kingdom.
Henry DanahayEnterprise Therapeutics, Sussex Innovation Centre, University of Sussex, Brighton, United Kingdom.
Tony RaynhamCRT Discovery Laboratories, Cambridge, United Kingdom.
Aurelie MousnierNational Heart and Lung Institute, Imperial College of Science, Technology and Medicine, London, United Kingdom.
Roberto SolariNational Heart and Lung Institute, Imperial College of Science, Technology and Medicine, London, United Kingdom r.solari@imperial.ac.uk.
Imperial College London · GBThe Pirbright Institute · GBQueen's University Belfast · GBUniversity of Sussex · GB

Funding

Biotechnology and Biological Sciences Research Council BB/L004828/1Medical Research Council G1000758Medical Research Council MC_PC_15028Medical Research Council MR/K020811/1Medical Research Council MR/M004821/1
6 · The paper itself

Abstract

Picornavirus replication is known to cause extensive remodeling of Golgi and endoplasmic reticulum membranes, and a number of the host proteins involved in the viral replication complex have been identified, including oxysterol binding protein (OSBP) and phosphatidylinositol 4-kinase III beta (PI4KB). Since both OSBP and PI4KB are substrates for protein kinase D (PKD) and PKD is known to be involved in the control of Golgi membrane vesicular and lipid transport, we hypothesized that PKD played a role in viral replication. We present multiple lines of evidence in support of this hypothesis. First, infection of HeLa cells with human rhinovirus (HRV) induced the phosphorylation of PKD. Second, PKD inhibitors reduced HRV genome replication, protein expression, and titers in a concentration-dependent fashion and also blocked the replication of poliovirus (PV) and foot-and-mouth disease virus (FMDV) in a variety of cells. Third, HRV replication was significantly reduced in HeLa cells overexpressing wild-type and mutant forms of PKD1. Fourth, HRV genome replication was reduced in HAP1 cells in which the PKD1 gene was knocked out by clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9. Although we have not identified the molecular mechanism through which PKD regulates viral replication, our data suggest that this is not due to enhanced interferon signaling or an inhibition of clathrin-mediated endocytosis, and PKD inhibitors do not need to be present during viral uptake. Our data show for the first time that targeting PKD with small molecules can inhibit the replication of HRV, PV, and FMDV, and therefore, PKD may represent a novel antiviral target for drug discovery.

Indexed as

AnimalsCell Line, TumorCricetinaeDNA ReplicationDNA, ViralFoot-and-Mouth Disease VirusGene Knockout TechniquesHeLa CellsHumansInterferon Type IPhosphorylationPoliovirusProtein Kinase CPyrimidinesRhinovirusVirus ReplicationCRT 0066101DNA, ViralInterferon Type IProtein Kinase Cprotein kinase DPyrimidinesantiviralGolgi membranepicornavirusprotein kinase Drhinovirusviral replication

Identifiers

PMID28228588
PMCPMC5391474
OpenAlexW2589456910

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.