Rhinovirus replication causes RANTES production in primary bronchial epithelial cells

The mechanisms by which rhinovirus (RV) infections produce lower airway sym ptoms in asthmatic individuals are not fully established. To determine effe cts of RV infection on lung epithelial cells, primary human bronchial epith elial (BE) cells were infected with either RV 16 or RV49, and viral replica tion, cell viability, and cell activation were measured. Both viral serotyp es replicated in BE cells at 33 degrees C (Delta TCID50/ml = 2 to 2.5 log u nits) and at 37 degrees C (Delta TCID50/ml = 1.6 log units), but only high doses of RV49 (10(6) TCID50/ml) caused cytopathic effects and reduced cell viability. In addition, regulated on activation, normal T cells expressed a nd secreted (RANTES) secretion was increased in epithelial cells infected w ith RV16 or RV49 (243 and 398 pg/ml versus 13 pg/ml uninfected control cell s), and a similar pattern was seen for RANTES messenger RNA. RV infection a lso caused increased secretion of interleukin-8 and granulocyte macrophage colony-stimulating factor, but did not alter expression of either intercell ular adhesion molecule-1 or human leukocyte-associated antigen-DR. These ob servations suggest that RVs can replicate in lower airway cells in vivo, an d support epidemiologic studies that link RV with lower respiratory illness es. Further, RV-induced secretion of RANTES and other cytokines could trigg er antiviral immune responses in vivo, but these effects could also contrib ute to the pathogenesis of respiratory symptoms in subjects with asthma.