eprintid: 10122156
rev_number: 12
eprint_status: archive
userid: 608
dir: disk0/10/12/21/56
datestamp: 2021-02-22 15:14:59
lastmod: 2021-02-22 15:19:17
status_changed: 2021-02-22 15:19:17
type: article
metadata_visibility: show
creators_name: Benedikz, EK
creators_name: Bailey, D
creators_name: Cook, CNL
creators_name: Gonçalves-Carneiro, D
creators_name: Buckner, MMC
creators_name: Blair, JMA
creators_name: Wells, TJ
creators_name: Fletcher, NF
creators_name: Goodall, M
creators_name: Flores-Langarica, A
creators_name: Kingsley, RA
creators_name: Madsen, J
creators_name: Teeling, J
creators_name: Johnston, SL
creators_name: MacLennan, CA
creators_name: Balfe, P
creators_name: Henderson, IR
creators_name: Piddock, LJV
creators_name: Cunningham, AF
creators_name: McKeating, JA
title: Bacterial flagellin promotes viral entry via an NF-kB and Toll Like Receptor 5 dependent pathway
ispublished: pub
divisions: UCL
divisions: A01
divisions: B02
divisions: C09
divisions: D11
divisions: G14
keywords: A549 Cells, Antigens, Bacterial, Bacterial Infections, Coinfection, Disease Susceptibility, Epithelial Cells, Flagellin, Gene Knockdown Techniques, HEK293 Cells, Host Microbial Interactions, Humans, Lung, Permeability, RNA, Small Interfering, Signal Transduction, Toll-Like Receptor 5, Transcription Factor RelA, Virus Diseases, Virus Internalization
note: This work is licensed under a Creative Commons Attribution 4.0 International License. The images
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unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license,
users will need to obtain permission from the license holder to reproduce the material. To view a copy of this
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abstract: Viruses and bacteria colonize hosts by invading epithelial barriers. Recent studies have shown that interactions between the microbiota, pathogens and the host can potentiate infection through poorly understood mechanisms. Here, we investigated whether diverse bacterial species could modulate virus internalization into host cells, often a rate-limiting step in establishing infections. Lentiviral pseudoviruses expressing influenza, measles, Ebola, Lassa or vesicular stomatitis virus envelope glycoproteins enabled us to study entry of viruses that exploit diverse internalization pathways. Salmonella Typhimurium, Escherichia coli and Pseudomonas aeruginosa significantly increased viral uptake, even at low bacterial frequencies. This did not require bacterial contact with or invasion of host cells. Studies determined that the bacterial antigen responsible for this pro-viral activity was the Toll-Like Receptor 5 (TLR5) agonist flagellin. Exposure to flagellin increased virus attachment to epithelial cells in a temperature-dependent manner via TLR5-dependent activation of NF-ΚB. Importantly, this phenotype was both long lasting and detectable at low multiplicities of infection. Flagellin is shed from bacteria and our studies uncover a new bystander role for this protein in regulating virus entry. This highlights a new aspect of viral-bacterial interplay with significant implications for our understanding of polymicrobial-associated pathogenesis.
date: 2019-05-27
date_type: published
official_url: https://doi.org/10.1038/s41598-019-44263-7
oa_status: green
full_text_type: pub
pmcid: PMC6536546
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1847586
doi: 10.1038/s41598-019-44263-7
pii: 10.1038/s41598-019-44263-7
lyricists_name: Madsen, Jens
lyricists_id: JMADS35
actors_name: Madsen, Jens
actors_id: JMADS35
actors_role: owner
full_text_status: public
publication: Scientific Reports
volume: 9
number: 1
article_number: 7903
event_location: England
citation:        Benedikz, EK;    Bailey, D;    Cook, CNL;    Gonçalves-Carneiro, D;    Buckner, MMC;    Blair, JMA;    Wells, TJ;                                                     ... McKeating, JA; + view all <#>        Benedikz, EK;  Bailey, D;  Cook, CNL;  Gonçalves-Carneiro, D;  Buckner, MMC;  Blair, JMA;  Wells, TJ;  Fletcher, NF;  Goodall, M;  Flores-Langarica, A;  Kingsley, RA;  Madsen, J;  Teeling, J;  Johnston, SL;  MacLennan, CA;  Balfe, P;  Henderson, IR;  Piddock, LJV;  Cunningham, AF;  McKeating, JA;   - view fewer <#>    (2019)    Bacterial flagellin promotes viral entry via an NF-kB and Toll Like Receptor 5 dependent pathway.                   Scientific Reports , 9  (1)    , Article 7903.  10.1038/s41598-019-44263-7 <https://doi.org/10.1038/s41598-019-44263-7>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10122156/1/Bacterial%20flagellin%20promotes%20viral%20entry%20via%20an%20NF-kB%20and%20Toll%20Like%20Receptor%205%20dependent%20pathway.pdf