Respiratory viral infections in children with asthma: do they matter and can we prevent them?

Ahanchian, Hamid; Jones, Carmen M; Chen, Yueh-sheng; Sly, Peter D

Respiratory viruses first infect nasal epithelial cells which triggers an antiviral response. This response is driven by type I (α/β) and III (λ) interferons (IFN) that are induced following recognition of viral ribonucleic acid (RNA) by pattern recognition receptors (PRRs). Toll-like receptors (TLRs) are cell surface and endosomal PRRs, whilst the RNA helicase receptors (RIG-I and MDA-5) and NODlike receptors (NOD2), detect viral RNA in the cytoplasm. Signalling via the PRRs activates transcription factors (IRF-3, IRF-7, NF-κB), which lead to the production and secretion of type I and III IFN. The IFNs then bind to cell surface receptors to activate a separate pathway leading to the production of interferon stimulated genes (ISGs) which encode antiviral proteins that combat infection, as well as PRRs and transcriptional factors which further amplify IFN production. The respiratory syncytial virus (RSV), human meta-pneumovirus (hMPV) and human rhinovirus (HRV) are all single stranded RNA viruses but engage differently with cell signalling pathways. In airway epithelial cells RSV and hMPV RNA are primarily detected by RIG-I in the cytoplasm [14, 15] . RSV can also be detected by NOD2 [16] . HRV is endocytosed by epithelial cells, and is therefore primarily detected by TLR3 in the endosome early in the infection process and by RIG-I and MDA-5 later in infection following upregulation of these PRRs [17] . The fusion (F) protein of RSV is recognised by TLR4 at the epithelial cell surface [18] .