Human metapneumovirus impairs apoptosis of nasal epithelial cells in asthma via HSP70 Baturcam, E, Snape, N, Yeo, TH, Schagen, J, Thomas, E, Logan, J, Galbraith, S, Collinson, N, Phipps, S, Fantino, E, Sly, Peter and Spann, KM 2017, Human metapneumovirus impairs apoptosis of nasal epithelial cells in asthma via HSP70, Journal of Innate Immunity, vol. 9, no. 1, pp. 52-64, doi: 10.1159/000449101. Attached Files Name Description MIMEType Size Downloads Title Human metapneumovirus impairs apoptosis of nasal epithelial cells in asthma via HSP70 Author(s) Baturcam, E Snape, N Yeo, TH Schagen, J Thomas, E Logan, J Galbraith, S Collinson, N Phipps, S Fantino, E Sly, Peter Spann, KM Journal name Journal of Innate Immunity Volume number 9 Issue number 1 Start page 52 End page 64 Total pages 13 Publisher Karger Place of publication Basel, Switzerland Publication date 2017-01 ISSN 1662-811X 1662-8128 Keyword(s) Apoptosis Asthma BURDEN CHILDREN DEFICIENT EXPRESSION Heat shock protein 70 HEAT-SHOCK PROTEINS Human metapneumovirus Immunology INFECTION INHIBITION Interferon Life Sciences & Biomedicine MECHANISM Primary nasal epithelial cells VIRUSES Science & Technology HEAT-SHOCK-PROTEIN-70 Summary Asthmatics are highly susceptible to respiratory viral infections, possibly due to impaired innate immunity. However, the exact mechanisms of susceptibility are likely to differ amongst viruses. Therefore, we infected primary nasal epithelial cells (NECs) from adults with mild-to-moderate asthma, with respiratory syncytial virus (RSV) or human metapneumovirus (hMPV) in vitro and investigated the antiviral response. NECs from these asthmatics supported elevated hMPV but not RSV infection, compared to non-asthmatic controls. This correlated with reduced apoptosis and reduced activation of caspase-9 and caspase-3/7 in response to hMPV, but not RSV. The expression of heat shock protein 70 (HSP70), a known inhibitor of caspase activation and subsequent apoptosis, was amplified in response to hMPV infection. Chemical inhibition of HSP70 function restored caspase activation and reduced hMPV infection in NECs from asthmatic subjects. There was no impairment in the production of IFN by NECs from asthmatics in response to either hMPV or RSV, demonstrating that increased infection of asthmatic airway cells by hMPV is IFN-independent. This study demonstrates, for the first time, a mechanism for elevated hMPV infection in airway epithelial cells from adult asthmatics and identifies HSP70 as a potential target for antiviral and asthma therapies. Language eng DOI 10.1159/000449101 Field of Research 11 Medical and Health Sciences HERDC Research category C1 Refereed article in a scholarly journal Free to Read? Yes Persistent URL http://hdl.handle.net/10536/DRO/DU:30164925 Document type: Journal Article Collections: Faculty of Health School of Medicine Open Access Collection Related Links Link Description Link to full-text (open access)   Connect to published version Go to link with your DU access privileges   Author URL Go to link with your DU access privileges   Connect to Elements publication management system Go to link with your DU access privileges     Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved. Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au. Versions Version Filter Type Mon, 21 Mar 2022, 08:35:42 EST Mon, 21 Mar 2022, 17:34:55 EST Wed, 06 Apr 2022, 09:04:01 EST Thu, 21 Apr 2022, 11:20:10 EST Thu, 21 Apr 2022, 14:25:43 EST Thu, 21 Apr 2022, 16:55:40 EST Thu, 05 May 2022, 22:38:27 EST Filtered Full Citation counts:   Cited 15 times in TR Web of Science Cited 15 times in Scopus Search Google Scholar Access Statistics: 11 Abstract Views, 0 File Downloads  -  Detailed Statistics Created: Mon, 21 Mar 2022, 08:35:42 EST