Nasopharyngeal gene expression, a novel approach to study the course of respiratory syncytial virus infection

Abstract

Respiratory syncytial virus (RSV) causes mild infections in the vast majority of children. However, in some cases, it causes severe disease, such as bronchiolitis and pneumonia. Development of severe RSV infection is determined by the host response. Therefore, the main aim of this study was to identify biomarkers associated with severe RSV infection.To identify biomarkers, nasopharyngeal gene expression was profiled by microarray studies, resulting in the selection of five genes: ubiquitin D, tetraspanin 8, mucin 13, β-microseminoprotein and chemokine ligand 7.These genes were validated by real-time quantitative PCR in an independent validation cohort, which confirmed significant differences in gene expression between mildly and severely infected and between recovery and acute patients.Nasopharyngeal aspirate samples are regularly taken when a viral respiratory tract infection is suspected. In this article, we describe a method to discriminate between mild and severe RSV infection based on differential host gene expression. The combination of pathogen detection and host gene expression analysis in nasopharyngeal aspirates will significantly improve the diagnosis and prognosis of respiratory tract infections. @ERSpublications Host gene expression analysis of nasopharyngeal aspirate samples can be used to predict RSV disease severity

Advancing our understanding of infant bronchiolitis through phenotyping and endotyping: clinical and molecular approaches

“…By investigating whole blood [43–46] and upper airway gene expression profiles [47], researchers demonstrated overexpression of interferon-related pathway in children with severe RSV infection compared to healthy controls or mild RSV infection. Furthermore, Mejias et al ., by examining whole blood transcriptome from children with severe bronchiolitis either by RSV, rhinovirus, or influenza in the U.S. and Finnish cohorts, observed pathogen-specific transcriptional signatures [43].…”

Mucosal IgG Levels Correlate Better with Respiratory Syncytial Virus Load and Inflammation than Plasma IgG Levels

“…Demographics and clinical parameters were collected from questionnaires and medical records. Within 24 h after admission, a blood sample and a nasopharyngeal aspirate (NPA) sample were collected as previously described (9). The mean age of the patients was 53 days, the average gestational age was 38 weeks, and 48% of the patients were male (Table 1).…”

Respiratory viral infections

“…Most respiratory viral mechanistic studies have been performed using influenza viruses, RSV, HRV and coronaviruses [80][81][82][83]. Using BEC, the common and demonstrated that the pattern of innate immune activation was both host cell and viral strain specific [85].…”

“…A number of studies have been undertaken to understand the pathogenesis of severe RSV in young children and have identified a variety of gene expression patterns in blood including under expression of T cell cytotoxicity/NK cells and plasma cell genes, as well as upregulation of JAK/STAT, prolactin, IL-9 signaling, cell to cell signaling, and immune activation pathways [79,92]. Using nasal epithelial gene expression analysis, van den Kieboom identified 5 differentially expressed genes in 30 children with mild, moderate and severe RSV infection [81]. Ubiquitin D, tetraspanin 8, mucin 13, β microseminoprotein, chemokine ligand 7 were up regulated and differentiated mild from severe illness.…”