Asthma exacerbations are commonly triggered by rhinovirus infections. Viruses can activate the NFkappaB pathway resulting in airway inflammation and increased Th2 cytokine expression. NFkappaB signaling is also involved in early activation of IFNbeta, which is a central mediator of antiviral responses to rhinovirus infection. Using a mouse model, this study tests our hypothesis that NFkappaB signaling is involved in impaired IFNbeta production at viral-induced asthma exacerbations. C57BL/6 wild-type and NFkappaB1-/- mice were challenged with house dust mite for 3 weeks and were subsequently stimulated with the rhinoviral mimic poly(I:C). General lung inflammatory parameters and levels of the Th2 upstream cytokine IL-33 were measured after allergen challenge. At exacerbation, production of IFNbeta and antiviral proteins as well as gene expression of pattern recognition receptors and IRF3/IRF7 was assessed. In the asthma exacerbation mouse model, lack of NFkappaB1 resulted in lower levels of IL-33 after allergen challenge alone and was associated with reduced eosinophilia. At exacerbation, mice deficient in NFkappaB1 exhibited enhanced expression of IFNbeta and antiviral proteins. This was accompanied by increased IRF3/IRF7 expression and induction of pattern recognition receptor expression. In a human asthma dataset, a negative correlation between IRF3 and NFkappaB1 expression was observed. NFkappaB may impair antiviral responses at exacerbation, possibly by reducing expression of the transcription factors IRF3/IRF7. These findings suggest a therapeutic potential for targeting NFkappaB pathways at viral infection-induced exacerbations.