Journal
JOURNAL OF INNATE IMMUNITY
Volume 9, Issue 1, Pages 52-64Publisher
KARGER
DOI: 10.1159/000449101
Keywords
Asthma; Primary nasal epithelial cells; Human metapneumovirus; Apoptosis; Interferon; Heat shock protein 70
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Funding
- National Health and Medical Research Council of Australia [1061921]
- Queensland Children's Medical Research Institute
- National Health and Medical Research Council of Australia [1061921] Funding Source: NHMRC
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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 meta-pneumovirus (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. (C) 2016 S. Karger AG, Basel
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