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Bacterial flagellin promotes viral entry via an NF-kB and Toll Like Receptor 5 dependent pathway

Bacterial flagellin promotes viral entry via an NF-kB and Toll Like Receptor 5 dependent pathway
Bacterial flagellin promotes viral entry via an NF-kB and Toll Like Receptor 5 dependent pathway

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.

2045-2322
Benedikz, Elizabeth K.
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Bailey, Dalan
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Cook, Charlotte N.L.
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Gonçalves-Carneiro, Daniel
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Buckner, Michelle M.C.
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Blair, Jessica M.A.
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Wells, Timothy J.
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Fletcher, Nicola F.
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Goodall, Margaret
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Flores-Langarica, Adriana
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Kingsley, Robert A.
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Madsen, Jens
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Teeling, Jessica
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Johnston, Sebastian L.
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MacLennan, Calman A.
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Balfe, Peter
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Henderson, Ian R.
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Piddock, Laura J.V.
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Cunningham, Adam F.
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McKeating, Jane A.
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Benedikz, Elizabeth K.
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Bailey, Dalan
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Cook, Charlotte N.L.
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Gonçalves-Carneiro, Daniel
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Buckner, Michelle M.C.
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Blair, Jessica M.A.
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Wells, Timothy J.
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Fletcher, Nicola F.
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Goodall, Margaret
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Flores-Langarica, Adriana
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Kingsley, Robert A.
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Madsen, Jens
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Teeling, Jessica
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Johnston, Sebastian L.
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MacLennan, Calman A.
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Balfe, Peter
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Henderson, Ian R.
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Piddock, Laura J.V.
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Cunningham, Adam F.
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McKeating, Jane A.
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Benedikz, Elizabeth K., Bailey, Dalan, Cook, Charlotte N.L., Gonçalves-Carneiro, Daniel, Buckner, Michelle M.C., Blair, Jessica M.A., Wells, Timothy J., Fletcher, Nicola F., Goodall, Margaret, Flores-Langarica, Adriana, Kingsley, Robert A., Madsen, Jens, Teeling, Jessica, Johnston, Sebastian L., MacLennan, Calman A., Balfe, Peter, Henderson, Ian R., Piddock, Laura J.V., Cunningham, Adam F. and McKeating, Jane A. (2019) Bacterial flagellin promotes viral entry via an NF-kB and Toll Like Receptor 5 dependent pathway. Scientific Reports, 9 (1), [7903]. (doi:10.1038/s41598-019-44263-7).

Record type: Article

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.

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s41598-019-44263-7 - Version of Record
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More information

Accepted/In Press date: 9 May 2019
e-pub ahead of print date: 27 May 2019
Published date: 1 December 2019

Identifiers

Local EPrints ID: 431785
URI: http://eprints.soton.ac.uk/id/eprint/431785
ISSN: 2045-2322
PURE UUID: 05fd75dc-b88a-4737-b369-b48c234a33d2
ORCID for Jens Madsen: ORCID iD orcid.org/0000-0003-1664-7645
ORCID for Jessica Teeling: ORCID iD orcid.org/0000-0003-4004-7391

Catalogue record

Date deposited: 17 Jun 2019 16:30
Last modified: 26 Nov 2021 02:52

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Contributors

Author: Elizabeth K. Benedikz
Author: Dalan Bailey
Author: Charlotte N.L. Cook
Author: Daniel Gonçalves-Carneiro
Author: Michelle M.C. Buckner
Author: Jessica M.A. Blair
Author: Timothy J. Wells
Author: Nicola F. Fletcher
Author: Margaret Goodall
Author: Adriana Flores-Langarica
Author: Robert A. Kingsley
Author: Jens Madsen ORCID iD
Author: Jessica Teeling ORCID iD
Author: Sebastian L. Johnston
Author: Calman A. MacLennan
Author: Peter Balfe
Author: Ian R. Henderson
Author: Laura J.V. Piddock
Author: Adam F. Cunningham
Author: Jane A. McKeating

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