Rhinovirus-Induced Exacerbations of Asthma and COPD

Abstract

Over the past two decades, increasing evidence has shown that, in patients with chronic airways disease, viral infection is the most common cause of exacerbation. This review will examine the evidence for viral-induced exacerbations of asthma and chronic obstructive lung disease and the potential mechanisms by which viruses cause exacerbations. Attention will be focused on rhinovirus, the most common cause of respiratory exacerbations. Exacerbations due to rhinovirus, which infects relatively few cells in the airway and does not cause the cytotoxicity of other viruses such as influenza or respiratory syncytial virus, are particularly poorly understood. While the innate immune response likely plays a role in rhinovirus-induced exacerbations, its precise role, either adaptive or maladaptive, is debated. Because current treatment strategies are only partially effective, further research examining the cellular and molecular mechanisms underlying viral-induced exacerbations of chronic airways diseases is warranted.

Figure 1

Images of bronchial epithelium from an adult subject without asthma who was experimentally infected with rhinovirus-16. (a) Hematoxylin and eosin stain shows an intact epithelium. (b) Tissue was stained for RV16 capsid protein (red) and DAPI, a nuclear stain. Note that some cells are stained with RV and others are not. (c) Tissue was stained with mouse IgG, a negative control, and DAPI. Note the absence of red staining. Antibody against RV16 and tissue blocks were generously provided by Wai-Ming Lee, Nizar Jarjour, and Jim Gern (University of Wisconsin).

Figure 2

A mechanism to explain defective innate immunity in asthma. The differentiation of Th1 and Th2 T-helper cell lineages is mutually antagonistic. Th2 cells produce IL-4 which blocks Th1 differentiation and Th1 cells produce IFN-γ which blocks Th2 differentiation. Thus, individuals with an immune system skewed towards Th2 tend not to produce eosinophils and IgE-producing B cells, but not Th1 cells. The relative lack of IFN-γ limits the antiviral response.

Figure 3

A mouse model of RV-induced asthma exacerbation. (a) Mature mice were sensitized with ovalbumin (OVA) and alum given intraperitoneally. This was followed by intranasal challenge with additional ovalbumin. One day after the last OVA challenge, animals were infected with RV1B, a minor group virus capable of infecting mouse cells. (b) Ovalbumin and RV1B have synergistic effects of airways responsiveness. Airways responsiveness was assessed by measuring changes in respiratory system resistance in response to increasing doses of nebulized methacholine. Respiratory system resistance was measured in anesthetized and endotracheally intubated mice using a computerized ventilator (Scireq, Montreal, Quebec, Canada).