Peroxisome proliferator-activated receptor-γ agonists inhibit the replication of respiratory syncytial virus (RSV) in human lung epithelial cells

We have previously shown that peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists inhibited the inflammatory response of RSV-infected human lung epithelial cells. In this study, we supply evidence that specific PPAR gamma agonists (15d-PGJ(2), ciglitazone, troglitazone. Fmoc-Leu) efficiently blocked the RSV-induced cytotoxicity and development of syncytia in tissue culture (A549, HEp-2). All PPAR gamma agonists under study markedly inhibited the cell surface expression of the viral G and F protein on RSV-infected A549 cells. This was paralleled by a reduced cellular amount of N protein-encoding mRNA determined by real-time RT-PCR. Concomitantly. a reduced release of infectious progeny virus into the cell supernatants of human lung epithelial cells (A549, normal human bronchial epithelial cells (NHBE)) was observed. Similar results were obtained regardless whether PPAR gamma agonists were added prior to RSV infection or thereafter. suggesting that the agonists inhibited viral gene expression and not the primary adhesion or fusion process. (c) 2006 Elsevier Inc. All rights reserved.