Children infected by rhinovirus (RV)-C are associated with more severe symptoms in their asthma exacerbation than those infected by RV-A. Study on the effect of RV-C infection on airway epithelia is limited due to difficulties in culturing RV-C. We hypothesized that the increased severity of RV-C infection is caused by a greater immune dysregulation of the asthmatic airway epithelial cell compared to RV-A.

In this study, the antiviral response in vivo was measured in nasopharyngeal aspirates (NPA) of the 29 RV-infected and hospitalized children. RV-A induced significantly higher expression of CCL5, CXCL10 and CXCL11 than patients with RV-C.

To understand the pathogenesis, the air-liquid interface (ALI) culture of the primary human bronchial epithelial cells was derived from the non-asthmatic donors for in vitro RV infection experiments followed by transcriptional profiling. In non-asthmatic adult HBEC ALI culture, a similar trend of antiviral gene induction by RV was observed. However, pathway enrichment in relation to cilium movement and assembly was significantly downregulated by RV-A16, including ARL6, IFT172 and DNALI1. In contrast, genes related to the MHC class II protein complex assembly pathway (e.g. HLA-DQA2, HLA-DMB and HLA-DPB1.) were stronger upregulated by RV-C15 infection.

In summary, we revealed that the antiviral gene induction pattern was similar between the NPA and in vitro cell model. Apart from a lower antiviral gene induction by RV-C, the altered antigen-presenting pathway would be the major driver of RV-C pathogenesis for the differential disease severities.

This study is supported by CUHK-Direct Grant 4054490 to R.W.Y.C.