The ABCs of rhinoviruses, wheezing, and asthma

Abstract

Human rhinoviruses (HRVs) were discovered as common cold pathogens over 50 years ago. Recent advances in molecular viral diagnostics have led to an appreciation of their role in more-significant respiratory illnesses, including bronchiolitis in infancy, childhood pneumonia, and acute exacerbations of chronic respiratory diseases such as asthma, chronic obstructive lung disease, and cystic fibrosis. Until a few years ago, only two groups of HRVs (A and B) had been recognized. However, full and partial sequencing of HRVs led to the discovery of a third species of HRV (HRV-C) that has distinct structural and biologic features. Risk factors and pathogenic mechanisms for more-severe HRV infections are being defined, and yet fundamental questions persist about mechanisms relating this common pathogen to allergic diseases and asthma. The close relationship between HRV infections and asthma suggests that antiviral treatments could have a major impact on the morbidity associated with this chronic respiratory disease.

FIG. 1.

HRV infection of bronchial epithelium. Before (A) and after (B) experimental infection of volunteers with HRV-16 in the nose, subjects underwent bronchoscopy, and biopsies of lower airway tissues (bronchial epithelium) were obtained. Immunohistochemistry was performed, using a monoclonal antibody (R16-7) specific for the VP0/VP2 capsid protein of HRV-16. Patchy cytoplasmic staining (purple) was observed in biopsies after viral inoculation (B). Cell nuclei are stained pale green. Modified from the American Journal of Respiratory and Critical Care Medicine (82) with permission of the publisher.

FIG. 2.

Relationship between HRV infections and asthma. Infants who develop virus-induced wheezing episodes are at increased risk for subsequent asthma, but even so, most acute wheezing illnesses in infancy resolve with no long-term sequelae. Indicators of heightened risk for developing asthma include wheezing episodes caused by HRV infections and the development of atopic features such as atopic dermatitis, allergen-specific IgE specific for foods or aeroallergens (e.g., house dust, mites, or cat or dog dander), and blood eosinophilia. Once asthma has been established, HRV infections are the most common cause of acute exacerbations, especially in children. As in infancy, atopy is an important risk factor for acute episodes of virus-induced wheezing.

FIG. 3.

Proposed effects of epithelial integrity on severity of HRV infections and exacerbations of asthma. (A) Intact airway epithelium is resistant to HRV infection. If the epithelium is healthy, exposure to HRV is less likely to initiate an infection, and if infection does occur, replication is at a low level and illness severity is mild. (B) Allergies and pollutants can damage the epithelium through a variety of mechanisms; allergy is associated with chronic cellular inflammation that can disrupt epithelial cells, while pollutants can have direct toxic effects on epithelial cells. When the epithelial layer is injured, exposure to HRV leads to enhanced viral replication and more-severe illness. In patients with asthma, severe colds are more likely than mild or asymptomatic infections to provoke acute exacerbations of asthma.