Induction of CD95 (Fas) and apoptosis in respiratory epithelial cell cultures following respiratory syncytial virus infection

Respiratory syncytial virus (RSV) infection is associated with epithelial c ell death and vigorous inflammation. In mouse models, and in immunosuppress ed patients, CD8(+) T cells are necessary for RSV clearance, in vitro, RSV has been shown to induce expression of several proteins on the respiratory epithelial cell, including RSV proteins, ICAM-1, and MHC class I, that can potentially interact with CD8(+) T cells in initiating apoptosis of the tar get cell. One mechanism of T-cell-directed cell death is the interaction of Fast on the CD8(+) T lymphocytes and Fas expressed on the target cell. In order to determine the ability of RSV to induce Fas on the respiratory epit helium, we studied the RSV infection of a human respiratory epithelial cell line (A549) in vitro. Fas mRNA and protein levels are increased two-to-fou rfold following RSV infection, and transcriptional upregulation of Fas was demonstrated using promoter/reporter gene constructs. RSV infection directl y resulted in cellular apoptosis, and the frequency of apoptotic cells was further increased by cross-linking with antibodies to Fas. These data demon strate that RSV infection induces cellular apoptosis and suggest that inter actions of surface Fas with T cells may further augment this process in viv o. (C) 1999 Academic Press.