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

Baturcam, E., Snape, N., Yeo, T.H., Schagen, J., Thomas, E., Logan, J., Galbraith, S., Collinson, N., Phipps, S., Fantino, E., Sly, P.D., and Spann, K.M. (2017) Human metapneumovirus impairs apoptosis of nasal epithelial cells in asthma via HSP70. Journal of Innate Immunity, 9 (1). pp. 52-64.

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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.

Item ID: 74893
Item Type: Article (Research - C1)
ISSN: 1662-8128
Keywords: Apoptosis, Asthma, Heat shock protein 70, Human metapneumovirus, Interferon, Primary nasal epithelial cells
Copyright Information: © 2016 S. Karger AG, Basel
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC project grant (No. 1061921)
Date Deposited: 12 Jul 2022 02:28
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3201 Cardiovascular medicine and haematology > 320103 Respiratory diseases @ 50%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3204 Immunology > 320404 Cellular immunology @ 20%
31 BIOLOGICAL SCIENCES > 3107 Microbiology > 310706 Virology @ 30%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200104 Prevention of human diseases and conditions @ 100%
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