Panou, M-M, Antoni, M, Morgan, EL et al. (5 more authors) (2020) Glibenclamide inhibits BK polyomavirus infection in kidney cells through CFTR blockade. Antiviral Research, 178. 104778. ISSN 0166-3542
Abstract
BK polyomavirus (BKPyV) is a ubiquitous pathogen in the human population that is asymptomatic in healthy individuals, but can be life-threatening in those undergoing kidney transplant. To-date, no vaccines or anti-viral therapies are available to treat human BKPyV infections. New therapeutic strategies are urgently required. In this study, using a rational pharmacological screening regimen of known ion channel modulating compounds, we show that BKPyV requires cystic fibrosis transmembrane conductance regulator (CFTR) activity to infect primary renal proximal tubular epithelial cells. Disrupting CFTR function through treatment with the clinically available drug glibenclamide, the CFTR inhibitor CFTR172, or CFTR-silencing, all reduced BKPyV infection. Specifically, time of addition assays and the assessment of the exposure of VP2/VP3 minor capsid proteins indicated a role for CFTR during BKPyV transport to the endoplasmic reticulum, an essential step during the early stages of BKPyV infection. We thus establish CFTR as an important host-factor in the BKPyV life cycle and reveal CFTR modulators as potential anti-BKPyV therapies.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 The Authors. Published by Elsevier B.V. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
Keywords: | PVAN; BK virus; Ion channel; Glibenclamide; CFTR |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Virology 2 (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Clinical Musculoskeletal Medicine (LIRMM) (Leeds) |
Funding Information: | Funder Grant number MRC (Medical Research Council) MR/K012665/1 Royal Society UF100419 Royal Society RG110306 |
Depositing User: | Symplectic Publications |
Date Deposited: | 20 Mar 2020 16:10 |
Last Modified: | 29 Mar 2022 04:54 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.antiviral.2020.104778 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:158565 |