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Could infection with different rhinovirus strains in infancy cause asthma?

Published online: April 25, 2020

Early-life wheezing-associated respiratory tract infections by human rhinovirus (RV) and respiratory syncytial virus (RSV) are considered risk factors for asthma development. Children are infected with many different RV strains, with infants having 6-10 distinct RV infections per year. RV infections do not induce specific immunity to reinfection by different serotypes, even if viruses are from the same species.  

In an Original Article recently published in The Journal of Allergy & Clinical Immunology (JACI), Rajput, Han and colleagues theorized that recurrent RV infections could result in greater degrees of airway inflammation and the potential for airway remodeling and loss of lung function over time. Six-day-old mice were infected with one serotype, RV-A1B, on day 6 of life, a different serotype, RV-A2, on day 13 of life, or both. Airway responses were measured one week after the second infection.  

As the authors showed previously (Hong J-Y, et al. JACI 2014), RV infection of 6-day-old mice induced migration of eosinophils to the airways and mucous overproduction similar to that seen in asthma. In contrast, infection of 13-day-old mice induced a mature antiviral response with airway neutrophils and no mucus. Finally, infection of 13-day-old mice with RV-A2 after earlier RV-A1B infection caused intensified eosinophil infiltration and mucous overproduction. Using mice deficient in retinoic acid receptor-related orphan receptor alpha, a transcription factor required for type 2 innate lymphoid cell (ILC2) development, the authors found that the asthma phenotype was dependent on ILC2s.

In summary, early-life infection with RV-A1B skewed the immune response to subsequent infection with RV-A2, causing an exaggerated asthma phenotype unrelated to increased viral load. These data provide a mechanism by which repeated RV infections in infancy could cause asthma.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

Graphical Abstract