Signaling pathways in the host cell response to RSV infection

Respiratory Syncytial Virus (RSV) is a negative-sense RNA virus of the family Paramyxoviridae and is responsible for significant numbers of human diseases. In children, RSV infection is a leading worldwide cause of severe lower respiratory tract infection (LRTI), clinically manifesting as pneumonia and bronchiolitis. RSV produce severe diseases in children with bronchopulmonary dysplasia, congenital heart disease, cystic fibrosis and immunosuppressed states. In natural infections, RSV primarily replicates in the airway mucosa, principally epithelial cells, where it activates an innate immune response via signaling pathways. Although many of the clinical manifestations of RSV are associated with an exaggerated host response to the virus, surprisingly RSV doesnot induce long term protective immunity even in normal hosts. For these reasons understanding RSV-induced cellular signaling pathways, the genetic response of epithelial cells to RSV, and how this virus modifies the cellular response will provide greater insights into how to therapeutically modify RSV-induced LRTI. This chapter reviews the impactof RSV disease, the processes it uses to replicate in airway epithelial cells, the signaling pathways responsive to this virus, and how nonstructural proteins modulate this process. Specifically we will focus on recent studies describing the role of the pattern recognition receptors (TLR), and the cytoplasmic RNA helicases (RIG-I) in modulatingtranscription factor activation including nuclear factor-κ B (NF-κ B) and the interferon response factor (IRF).