RESPIRATORY SYNCYTIAL VIRUS-INDUCED RANTES PRODUCTION FROM HUMAN BRONCHIAL EPITHELIAL-CELLS IS DEPENDENT ON NUCLEAR FACTOR-KAPPA-B NUCLEAR-BINDING AND IS INHIBITED BY ADENOVIRUS-MEDIATED EXPRESSION OF INHIBITOR OF KAPPA-B-ALPHA

Respiratory syncytial virus (RSV) infection is an important cause of l ower respiratory tract illness, the severity of which may be partly du e to cellular recruitment. RSV infection activates chemokine secretion from airway epithelial cells by largely unknown mechanisms. We invest igated the regulation of RSV-induced activation of the chemokine RANTE S in the bronchial epithelial cell line BEAS-2B and primary normal hum an tracheobronchial epithelial cultures. RANTES protein and mRNA were detected at 24 h and up until 72 h from cultures of BEAS-2B infected w ith replicating virus, but not with UV-inactivated RSV, RSV infection of BEAS-2B or normal human tracheobronchial epithelial cells stimulate d NF-kappa B translocation to the nucleus and binding to the RANTES-sp ecific kappa B-binding sequences within 2 h, with levels peaking at 24 h, Supershift assays indicated that binding was due to p50/p65 hetero dimers. BEAS-2B cells were transfected with a replication-deficient ad enoviral vector, expressing a mutated, nondegradable form of I kappa B alpha. I kappa B alpha overexpression specifically blocked NF-kappa B translocation and inhibited mRNA accumulation and secretion of RANTES induced by RSV or TNF-alpha plus IFN-gamma. Adenoviral transfection d id not interfere with RSV replication or significantly induce apoptosi s, Further, a control adenovirus, expressing the beta-galactosidase ge ne, did not alter cellular functions. Thus, NF-kappa B nuclear translo cation is a critical step in RSV induction of RANTES secretion. Elucid ating the mechanisms of cellular activation by RSV and targeting speci fic areas may lead to novel therapeutic approaches in the treatment of RSV.