Viral induction of a chronic asthma phenotype and genetic segregation from the acute response

Area of Science:

• Immunology
• Virology
• Respiratory Medicine

Background:

• Paramyxoviruses are a leading cause of acute lower respiratory tract illness in young children.
• The link between short-term viral infections and long-term respiratory conditions like chronic wheezing remains unclear.
• Understanding these viral effects is crucial for managing lifelong airway diseases such as asthma.

Purpose of the Study:

• To investigate the relationship between acute paramyxoviral infection and the development of chronic airway hyperreactivity.
• To elucidate the distinct immunological pathways involved in acute and chronic responses to paramyxovirus.
• To determine the role of ICAM-1 and IFN-gamma in paramyxovirus-induced airway inflammation and hyperreactivity.

Main Methods:

• A single paramyxoviral infection was induced in C57BL6/J mice and ICAM-1-null mice.
• Airway inflammation, hyperreactivity, and goblet cell hyperplasia were assessed during acute and chronic phases.
• The influence of IFN-gamma deficiency and glucocorticoid treatment on these responses was evaluated.

Main Results:

• Paramyxoviral infection caused acute bronchiolitis and a chronic response with airway hyperreactivity and goblet cell hyperplasia lasting over a year.
• ICAM-1-null mice were protected from acute inflammation but not the chronic response, indicating distinct mechanisms.
• IFN-gamma deficiency did not affect either response, while glucocorticoids partially prevented the chronic response.

Conclusions:

• Paramyxoviruses induce both acute airway inflammation/hyperreactivity and chronic airway remodeling/hyperreactivity phenotypes.
• These phenotypes are mediated by distinct, separable controls, with ICAM-1 playing a role in the acute but not chronic phase.
• Paramyxoviral infections may act via a 'hit-and-run' mechanism, contributing to the development of lifelong airway diseases like asthma.