Abstract
Rationale The respiratory epithelium comprises polarized cells at the interface between the environment and airway tissues. Polarized apical and basolateral protein secretions are a feature of airway epithelium homeostasis. Human respiratory syncytial virus (hRSV) is a major human pathogen that primarily targets the respiratory epithelium. However, the consequences of hRSV infection on epithelium secretome polarity and content remains poorly understood. Objective To investigate the impact of hRSV on the secretome of pediatric respiratory epithelium. Methods A proteomics approach was combined with an ex-vivo pediatric airway epithelial model (HAE) (n=3 donors) of hRSV infection to identify the apical and basolateral secretome of hRSV-infected cultures. Measurements and main results Following hRSV infection, many host proteins lost their apical- or basolateral-restricted secretion or displayed altered apical/basolateral abundance ratios. Fifty three proteins were specifically associated with RSV infection, including modulators of neutrophil and lymphocyte activation (CXCL6, CSF3, SECTM1 or CXCL16), and antiviral proteins (BST2 or CEACAM1) that were never previously associated with hRSV. Importantly, CXCL6, CXCL16, CSF3 was also detected in nasopharyngeal aspirates (NPA) from hRSV-infected infants but not non-infected controls. Furthermore, the antiviral activity of CEACAM1 against RSV was confirmed in vitro using BEAS-2B cells. Conclusions hRSV infection disrupted the polarity of the pediatric respiratory epithelial secretome. It also specifically induced immune modulating (CXCL6, CXCL16, CSF3) and an antiviral protein (CEACAM1) that are new to hRSV infection or disease. This study, therefore, provides novel insights into RSV pathogenesis and endogenous antiviral responses in pediatric airway epithelium.
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