Genetic Susceptibility to Respiratory Syncytial Virus Bronchiolitis Is Predominantly Associated with Innate Immune Genes

Abstract

SNPs in innate immune genes are important in determining susceptibility to RSV bronchiolitis.

Interleukin-15 is associated with disease severity in viral bronchiolitis

“…Immunoparesis in this context may be genetically mediated and may, at least in part, account for the inherited susceptibility to severe bronchiolitis seen among some children [28]. Support for this hypothesis comes from genetic association studies undertaken and published by our colleagues in Utrecht, The Netherlands [6]. In one of the biggest studies of its kind, JANSSEN et al [6] showed an overall association of innate immunity genes with genetic susceptibility to RSV infection in a candidate gene study of 480 hospitalised children and >1000 controls.…”

“…Support for this hypothesis comes from genetic association studies undertaken and published by our colleagues in Utrecht, The Netherlands [6]. In one of the biggest studies of its kind, JANSSEN et al [6] showed an overall association of innate immunity genes with genetic susceptibility to RSV infection in a candidate gene study of 480 hospitalised children and >1000 controls. Among other associated loci, they showed a nominal association with alleles of the IL15 gene variant rs2254514 (OR 1.22, 95% CI 1.02-1.46; p=0.026) and hospitalisation for RSV.…”

“…IL-15, in particular, regulates NK cell development and activation state [16,17], and has previously been linked with the risk of hospitalisation for viral bronchiolitis [6,18]. Preliminary work examining a panel of innate cytokines in viral bronchiolitis also demonstrated a relationship between IL-15 levels and disease [19].…”

Genetic variation associates with susceptibility for cigarette smoke-induced neutrophilia in mice

“…Expression of Ifna5, encoding a type I interferon with known high expression in bronchial epithelial cells (35), was not significantly affected by CS exposure. Although no correlation was found between gene expression level and CS-induced neutrophilic airway inflammation, Ifna5 was found previously to be associated with respiratory syncytial virus-induced bronchiolitis, a disease that shares some similarities with CS-induced airway inflammation (22). Moreover, IFN-␣ molecules are known inducers of apoptosis by ligating the interferon-␣ receptor (12,18).…”

What is the evidence of a role for host genetics in susceptibility to influenza A/H5N1?

“…Cytokine dysregulation has been shown to be a feature of A/H5N1 infection in clinical and animal studies [59][60][61] and various aspects of innate immunity including collectin-like mannose-binding lectin, tolllike receptors (TLR 3,7,8), cytokines, chemokines, and interferon-inducible proteins such as MxA are also plausible candidates [62][63][64][65][66][67][68]. Interestingly, susceptibility to other viral respiratory pathogens has been traced to genes of the innate immune system [69][70][71][72][73].…”