Human metapneumovirus impairs apoptosis of nasal epithelial cells in asthma via HSP70

Baturcam, Engin, Snape, Natale, Yeo, Tiong Han, Schagen, Johanna, Thomas, Emma, Logan, Jayden, Galbraith, Sally, Collinson, Natasha, Phipps, Simon, Fantino, Emmanuelle, Sly, Peter D. and Spann, Kirsten M. (2016) Human metapneumovirus impairs apoptosis of nasal epithelial cells in asthma via HSP70. Journal of Innate Immunity, 9 1: 52-64. doi:10.1159/000449101


Author Baturcam, Engin
Snape, Natale
Yeo, Tiong Han
Schagen, Johanna
Thomas, Emma
Logan, Jayden
Galbraith, Sally
Collinson, Natasha
Phipps, Simon
Fantino, Emmanuelle
Sly, Peter D.
Spann, Kirsten M.
Title Human metapneumovirus impairs apoptosis of nasal epithelial cells in asthma via HSP70
Journal name Journal of Innate Immunity   Check publisher's open access policy
ISSN 1662-8128
1662-811X
Publication date 2016-10-11
Year available 2017
Sub-type Article (original research)
DOI 10.1159/000449101
Open Access Status Not yet assessed
Volume 9
Issue 1
Start page 52
End page 64
Total pages 13
Place of publication Basel, Switzerland
Publisher S. Karger AG
Language eng
Abstract 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.
Keyword Apoptosis
Asthma
Heat shock protein 70
Human metapneumovirus
Interferon
Primary nasal epithelial cells
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 1061921
Institutional Status UQ

 
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