Zhuang, Xiaodong, Gallo, Giulia, Sharma, Parul, Ha, Jiyeon, Magri, Andrea, Borrmann, Helene, Harris, James M, Tsukuda, Senko, Bentley, Eleanor, Kirby, Adam et al (show 10 more authors)
(2024)
Hypoxia inducible factors inhibit respiratory syncytial virus infection by modulation of nucleolin expression.
iScience, 27 (1).
108763-.
Abstract
Respiratory syncytial virus (RSV) is a global healthcare problem, causing respiratory illness in young children and elderly individuals. Our knowledge of the host pathways that define susceptibility to infection and disease severity are limited. Hypoxia inducible factors (HIFs) define metabolic responses to low oxygen and regulate inflammatory responses in the lower respiratory tract. We demonstrate a role for HIFs to suppress RSV entry and RNA replication. We show that hypoxia and HIF prolyl-hydroxylase inhibitors reduce the expression of the RSV entry receptor nucleolin and inhibit viral cell-cell fusion. We identify a HIF regulated microRNA, miR-494, that regulates nucleolin expression. In RSV-infected mice, treatment with the clinically approved HIF prolyl-hydroxylase inhibitor, Daprodustat, reduced the level of infectious virus and infiltrating monocytes and neutrophils in the lung. This study highlights a role for HIF-signalling to limit multiple aspects of RSV infection and associated inflammation and informs future therapeutic approaches for this respiratory pathogen.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Molecular biology, Omics, Transcriptomics; |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 31 Jan 2024 11:50 |
| Last Modified: | 31 Jan 2024 11:50 |
| DOI: | 10.1016/j.isci.2023.108763 |
| Open Access URL: | https://doi.org/10.1016/j.isci.2023.108763 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3178192 |
Dimensions
Dimensions
