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

Benedikz, EK; Bailey, D; Cook, CNL; Gonçalves-Carneiro, D; Buckner, MMC; Blair, JMA; Wells, TJ; ... McKeating, JA; + view all (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. Green open access

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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.

Type: Article
Title: Bacterial flagellin promotes viral entry via an NF-kB and Toll Like Receptor 5 dependent pathway
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41598-019-44263-7
Publisher version: https://doi.org/10.1038/s41598-019-44263-7
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, 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 license, visit http://creativecommons.org/licenses/by/4.0/
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
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Neonatology
URI: https://discovery.ucl.ac.uk/id/eprint/10122261
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