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

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

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6 Citations (Scopus)
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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.

Original languageEnglish
Article number7903
JournalScientific Reports
Issue number1
Publication statusPublished - 27 May 2019


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