COPD Is Associated with Elevated IFN-β Production by Bronchial Epithelial Cells Infected with RSV or hMPV.

Natasha Collinson,Kenneth Beagley,Emmanuelle Fantino,Kirsten Spann,Natale Snape

doi:10.3390/v13050911

Abstract

IFN treatment may be a viable option for treating COPD exacerbations based on evidence of IFN deficiency in COPD. However, in vitro studies have used primarily influenza and rhinoviruses to investigate IFN responses. This study aims to investigate the susceptibility to infection and IFN response of primary bronchial epithelial cells (BECs) from COPD donors to infection with RSV and hMPV. BECs from five COPD and five healthy donors were used to establish both submerged monolayer and well-differentiated (WD) cultures. Two isolates of both RSV and hMPV were used to infect cells. COPD was not associated with elevated susceptibility to infection and there was no evidence of an intrinsic defect in IFN production in either cell model to either virus. Conversely, COPD was associated with significantly elevated IFN-β production in response to both viruses in both cell models. Only in WD-BECs infected with RSV was elevated IFN-β associated with reduced viral shedding. The role of elevated epithelial cell IFN-β production in the pathogenesis of COPD is not clear and warrants further investigation. Viruses vary in the responses that they induce in BECs, and so conclusions regarding antiviral responses associated with disease cannot be made based on single viral infections.

Highlights

Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death worldwide [1]
bronchial epithelial cells (BECs) from COPD donors displayed a trend of less viral shedding compared to healthy BECs in response to all viruses tested in this study (Figure 1)
This trend was clearer in response to the two human metapneumovirus (hMPV) isolates (Figure 1a,b; days 3 and 5) compared to the two respiratory syncytial virus (RSV) isolates—only hMPV AUS-001 elicited a significant difference between healthy and COPD BECs at day 5 p.i./mL, COPD

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is currently the third leading cause of death worldwide [1]. An estimated 328 million people suffer from COPD, positioning this disease as a leading cause of morbidity and mortality globally [2,3]. The progression of COPD, the frequency of exacerbations requiring hospitalisation, and the commonality of co-morbidities such as heart disease affect quality of life for patients and place enormous strain on the global healthcare economy [4]. Viral infections are a major cause of hospitalisation for COPD exacerbations [5]. In patients with COPD, the same viral infections are more severe and more likely to spread to the lower airways, causing exacerbation of the disease [6,7,8]. HMPV is emerging as an exacerbator of COPD, a global neglect to test for this virus in the adult population has delayed recognition [10,11]

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