TABLE 1.
Summary of literature evidence of potential viral induced exacerbation mechanisms in chronic airway inflammatory diseases at the upper airway epithelium.
Types of exacerbation mechanism | Viral specific trait contributing to exacerbation mechanism (with literature evidence) |
Increased viral susceptibility and prolonged activation of inflammation | Weak type 1 inflammation leading to skewed type 2 inflammation (RV, RSV) Persistence of virus and viral components (RV, RSV, AdV, hCMV, HSV) Development of steroid resistance (RV, RSV, PIV) |
Destruction of the epithelial barrier | Diffused cell death in the epithelial layer (IFV, CoV) |
Augmentation of infiltration by increasing barrier leakiness | Disruption of tight junctions (RV, RSV) Oncostatin M induction (IFV) ANGPTL4 induction (IFV) BPIFA1 changes (IFV) |
Alteration of airway microbiome | Destabilization of the microbiome (RV) Disruption of biofilm colonies (IFV) Alteration of the airway nutrient profile (RV, IFV) Reduced bacterial immunity (RV, possibly IFV and RSV) |
Disruption of mucociliary functions and balance | Infection targeting ciliated cells (RV, IFV, RSV) Alteration of ciliary gene expression (IFV) Destruction of cilia and disruption of ciliary function (RSV, CoV) Mucus overproduction (RV) |
miRNA and other epigenetic modulation of inflammation | miRNA modulation (IFV, RV, RSV) DNA methylation and histone modifications (RV, RSV) |
Oxidative stress | ROS production (RV, RSV, IFV, HSV) |
As RV, RSV, and IFV were the most frequently studied viruses in chronic airway inflammatory diseases, most of the viruses listed are predominantly these viruses. However, the mechanisms stated here may also be applicable to other viruses but may not be listed as they were not implicated in the context of chronic airway inflammatory diseases exacerbation (see text for abbreviations).