INFECTION OF A HUMAN RESPIRATORY EPITHELIAL-CELL LINE WITH RHINOVIRUS- INDUCTION OF CYTOKINE RELEASE AND MODULATION OF SUSCEPTIBILITY TO INFECTION BY CYTOKINE EXPOSURE

Rhinovirus infections cause over one third of all colds and are a cont ributing factor to exacerbations of asthma. To gain insights into the early biochemical events that occur in infected epithelial cells, we d evelop, for the first time, a model in which a pure respiratory epithe lial cell population can be routinely infected by rhinovirus. Viral in fection was confirmed by demonstrating that viral titers of supernatan ts and lysates from infected cell increased with time and by PCR, Infe ction by rhinovirus 14 was inhibited by homotypic antiserum and by ant ibodies to intercellular adhesion molecule-1 (ICAM-1), the receptor fo r this virus. Susceptibility of epithelial cells to infection by rhino virus 14 (but not rhinovirus 2, an ICAM-1 independent strain) can be i ncreased by preexposure of cells to TNF alpha, whereas IFN gamma reduc es susceptibility to infection by both rhinovirus strains. Rhinovirus infection per se does not markedly alter ICAM-1 expression on epitheli al cells. Finally, we demonstrate that rhinovirus infection induced in creased production of IL-8, IL-6, and GM-CSF from epithelial cells. Pr oduction of IL-8 correlated with viral replication during the first 24 h after infection. This model should provide useful insights into the pathogenesis of rhinovirus infections.