Respiratory Syncytial Virus induces distinct interferon signatures in alveolar and bronchial epithelial cell lines

Friday, November 08, 2013 — Poster Session IV
2:00 p.m. – 4:00 p.m.	FAES Academic Center (Upper-Level Terrace)	FDA/CBER	IMMUNO-25

Authors

R.E. Shepard
P. Hillyer
F. Sheikh
C. Luongo
P.L. Collins
R.P. Donnelly
R.L. Rabin

Abstract

Respiratory Syncytial Virus (RSV) causes infantile bronchiolitis and pneumonia, which can be severe or even fatal. RSV targets the pulmonary epithelium, which rapidly expresses IFN-Beta and IFN-Lambda, types I and III interferons (IFN), respectively. These IFN induce expression of interferon stimulated genes (ISG), many of which code for antiviral defense proteins. We asked whether less effective IFN or ISG expression, in addition to the diseases’ anatomic locations, may contribute to the comparative severity of RSV pneumonia versus bronchiolitis. We therefore infected the BEAS-2B (bronchial) and A549 (alveolar) epithelial cell lines with GFP-RSV at MOI = 0.1 to monitor differences in cell-to-cell spread of infection and IFN-ISG response. While BEAS-2B cells contained the GFP-RSV within foci of ~10-15 cells, all of the A549 cells were infected by 48h. Both cell lines highly expressed IFN-Beta and IFN-Lambda, but A549 expressed more of each, and had more STAT1/STAT2 phosphorylation. Paradoxically, A549 expressed antiviral ISG at either similar (OAS1) or lower levels (ISG15) than BEAS-2B. Our data suggest that these comparative studies will point to differential patterns of expression of antiviral ISG that critically protect against local spread of RSV.