Genes Associated with RSV Lower Respiratory Tract Infection and Asthma: The Application of Genetic Epidemiological Methods to Understand Causality

Abstract

Infants with respiratory syncytial virus (RSV) lower respiratory tract infections (LRIs) are at increased risk for childhood asthma. The objectives of this article are to review the genes associated with both RSV LRI and asthma, review analytic approaches to assessing shared genetic risk and propose a future perspective on how these approaches can help us to understand the role of infant RSV infection as both an important risk factor for asthma and marker of shared genetic etiology between the two conditions. The review of shared genes and thus pathways associated with severity of response to RSV infection and asthma risk can help us to understand mechanisms of disease and ultimately propose new and novel targets for primary prevention of both diseases.

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

“…However, the limited literature suggests a relationship of host genetics with susceptibility and severity of bronchiolitis [36]. For example, a Danish twin study documented that genetic factors account for 16% of the individual susceptibility to develop severe RSV bronchiolitis [37].…”

“…For example, a Danish twin study documented that genetic factors account for 16% of the individual susceptibility to develop severe RSV bronchiolitis [37]. Although no genome-wide association study (GWAS) has examined bronchiolitis, candidate gene association studies have provided evidence for genes that increase the severity of RSV infection along many biological pathways, such as innate immunity, adaptive immunity, chemotaxis, airway epithelial response, and known allergic asthma genes [36,38,39]. For example, Janssen et al ., by examining 384 single-nucleotide polymorphisms from 220 genes involved in immune responses, found that genes from innate immune pathway are important in RSV infection severity [40].…”

Using urine metabolomics to understand the pathogenesis of infant respiratory syncytial virus (RSV) infection and its role in childhood wheezing

“…Recent developments in high-throughput molecular techniques provide an opportunity for understanding pathogenesis of RSV infection, but a biomarker that accurately and consistently predicts susceptibility to RSV infection, infection severity, and association with subsequent development of persistent wheezing and asthma has yet to be developed (Larkin and Hartert 2015; Openshaw 2013; Rosas-Salazar et al 2015). Metabolic pathways, as a mirror of the interactions between host cell and virus (Pearce and Pearce 2013; Peeples and Levine 1980), provide an opportunity to understand the mechanisms that underlie severe infections and pathways through which RSV ARI contributes to the development of asthma.…”

The Absence of Interferon-β Promotor Stimulator-1 (IPS-1) Predisposes to Bronchiolitis and Asthma-like Pathology in Response to Pneumoviral Infection in Mice

“…Unsurprisingly, genetic variants of various virus-sensing PRRs and anti-viral mediators are associated with an increased risk of severe RSV bronchiolitis 10–12 . This includes members of the endosomal toll-like receptor family such as TLR7 12 and members of the type-I IFN family such as IFNA5 13 .…”