Respiratory syncytial virus infection induces expression of the anti-apoptosis gene IEX-1L in human respiratory epithelial cells.
By means of differential display reverse-transcriptase polymerase chain reaction, increased expression of the mRNA encoding the anti-apoptosis gene IEX-1L was found in respiratory epithelial cells infected with respiratory syncytial virus (RSV). IEX-1L mRNA expression increased 5-7-fold in RSV-infected cells at 72 h after infection but remained unchanged in cells exposed to irradiated, replication-incompetent RSV. Because IEX-1L is reported to protect cells from apoptosis induced by tumor necrosis factor (TNF)-alpha, the effect of TNF-alpha on epithelial cell apoptosis in the context of RSV infection was determined. Epithelial cells were exposed to vehicle, RSV, or irradiated RSV for 72 h, and then TNF-alpha was added to appropriate cultures. Cytochemical staining of cellular DNA with 4,6-diamidino-2-phenylindole demonstrated TNF-alpha-induced apoptosis in 23.4% of control cells but only 5% of RSV-infected cells. These data show that RSV infection protects epithelial cells from TNF-alpha-induced apoptosis and that this effect is temporally associated with IEX-1L gene expression.
Domachowske
J B
JB
Department of Pediatrics, Division of Infectious Disease, Upstate Medical University, Syracuse, NY 13210, USA. domachoj@vax.cs.hscsyr.edu
Bonville
C A
CA
Mortelliti
A J
AJ
Colella
C B
CB
Kim
U
U
Rosenberg
H F
HF
D000256:Adenoviridae / Q000502:physiology; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D005786:Gene Expression Regulation; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics*; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger / Q000032:analysis; D012136:Respiratory Syncytial Viruses / Q000502:physiology* / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation
D051017:Apoptosis Regulatory Proteins; C099815:IER3 protein, human; D017874:Immediate-Early Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha