Background: Human rhinoviruses (HRV) infect epithelial cells in the respiratory track and cause relatively mild cold symptoms in most of the population. However, in children with asthma, HRV infection is associated with more severe asthma exacerbations that necessitate hospitalisation. Currently, it is not known why asthmatic children are more susceptible to HRV induced disease. To further our understanding of the mechanisms that underlie HRV induced allergic asthma exacerbations; we established a rat model of viral infection and compared the antiviral early immune response in asthma-prone BN rats versus asthma resistant PVG rats.
Objective: The objective of this study is to employ systems biology tools to determine how asthma-prone and asthma resistant rats respond to respiratory viral infection.
Methods: Naïve male PVG or BN rats were infected with virus via intranasal inoculation. At 24 hours post-infection, airway inflammatory cells were obtained from the bronchoalveolar lavage (BAL) fluid. Gene expression patterns in the airway inflammatory cells were profiled on microarrays. Differentially expressed genes were identified, and mapped onto biological pathways and networks.
Results: In PVG rats, 323 genes were upregulated after viral infection, and 30 were downregulated. In contrast, 99 genes were upregulated and 189 genes were downregulated following viral infection in the BN rats. Pathways analysis demonstrated that the PVG responses were characterised by upregulation of genes involved in T cell activation, and Th1 and antiviral signalling pathways (IL-15, IL-21, type I interferons). Strikingly, these same pathways were downregulated in the responses of the BN rats. These findings were validated by real-time RT-PCR.
Conclusion: Antiviral responses in asthma resistant PVG rats are associated with upregulation of Th1 and type I interferon-signalling pathways, and a reciprocal pattern was observed in asthma-prone BN rats. These data suggest that deficient activation of Th1 and interferon responses to viral infection may underlie susceptibility of asthmatic children to HRV.