Using integrated omics to assess the effects of rhinovirus infection in children with Cystic Fibrosis (CF)

Introduction/Aim: Children with Cystic Fibrosis (CF) typically exhibit prolonged and severe symptoms during rhinovirus (RV) infection compared to healthy children. Here, we studied the host-rhinovirus interaction signature after infection, integrating two omics: (1) Whole transcriptome sequencing (WTS) to determine the viral load and host’s gene expression, and (2) metabolomics to profile the metabolites associated with the viral infection of primary tracheal epithelial cells obtained from healthy children (H) and those with CF. Methods: WTS and hydrophilic interaction liquid chromatography (HILIC) coupled to mass spectrometry, were used to identify the differences in transcripts/metabolites and RV coverage produced by H (3.9 ± 1.5 years; n=8) and CF (2.6 ± 1.8 years; n=8; all p.Phe508del/p.Phe508del) primary epithelial cells at 24 hours post-infection with human rhinovirus 1B. Univariate and multivariate analyses were then performed to identify the infection hallmark. Results: RV coverage in uninfected cells (Mock) was less than 0.5X, whereas, infected cells presented 44.4X and 101.6X of RV in children with and without CF respectively. Global RV infection was associated with 14 metabolites and 1713 genes differential expressed. From these, several metabolic pathways were found dysregulated including inositol metabolism and glycerophospholipid biosynthesis. Conclusion: Metabolic host-derived pathways associated with RV infection were identified. Although functional analysis is still required, these pathways could be used as potential biomarkers of RV infection in CF. Future analysis will help to understand whether these compounds can be targeted for antiviral purposes.