Rhinovirus (RV) infections are normally controlled by robust antiviral responses and tightly regulated innate immune responses. However, many asthmatics display exaggerated lung inflammation and suboptimal interferon (IFN) production in response to RV. Using whole mouse transcriptome array analyses following RV1B infection in non-allergic mice, we identified CCL7 and IRF-7 as two of the most up-regulated mRNA transcripts. To investigate their roles we infected naïve BALB/c mice (non-allergic) and mice with allergic airways disease, induced by house dust mite (allergic) with RV1B in conjunction with anti-CCL7 antibodies and an IRF-7-targeted siRNAs. At one day post-RV infection, we observed significant increase in CCL7, CCL11, CCL20 and CXCL2 in the lung, as well as neutrophil and macrophage recruitment in bronchoalveolar lavage fluid in positive control mice treated with non-targeting isotype control antibodies or nonsense siRNA. IFN-a and -b were also produced concurrent with IRF-3, -5, and -7 expression. Neutralising CCL7 or inhibiting IRF-7 limited neutrophil and macrophage influx and IFN responses in non-allergic mice. Neutralising CCL7 reduced NF-κB p65 and p50 subunit activity, as well as airways hyperreactivity (AHR) in non-allergic mice. However, neither NF-κB subunit activation nor AHR were abolished in allergic mice after anti-CCL7, despite reduced numbers of neutrophils, macrophages and eosinophils. IRF-7 siRNA primarily suppressed IFN-a and -b levels during infection of allergic mice. Our data highlights a pivotal role of CCL7 in RV-induced inflammation and IRF-7 in RV-induced IFN responses, which in the presence of allergic airways disease, are dissociated from NF-κB signalling and AHR.