Cytokeratin 17 is expressed in cells infected with respiratory syncytial virus via NF-kappaB activation and is associated with the formation of cytopathic syncytia.
We used differential display to detect enhanced expression of an mRNA fragment encoding cytokeratin 17 (Ck-17) in respiratory syncytial virus (RSV)-infected epithelial cells. Expression increased 12-fold by 96 h after infection but remained unchanged in cells challenged with virus in the presence of neutralizing anti-RSV fusion protein antibody. Immunoblots of RSV-infected cell lysates probed with an anti-keratin antibody demonstrated stable expression of total cytokeratins over time. When probed with an anti-Ck-17 monoclonal antibody, Ck-17 was first detected at 4 days after infection. In situ staining demonstrated that Ck-17 expression localized to regions of syncytia formation. Expression of Ck-17 mRNA also increased in response to intracellular RSV-F protein in the absence of active RSV infection. No increase in Ck-17 mRNA expression and no syncytia were observed in RSV-infected cells grown in the presence of the NF-kappaB inhibitor gliotoxin. These results suggest that RSV-induced transcriptional activation of the Ck-17 gene is dependent on an NF-kappaB-associated signaling pathway.
Domachowske
J B
JB
Department of Pediatrics, Division of Infectious Disease, SUNY Upstate Medical University, Syracuse, NY 13210, USA. domachoj@upstate.edu
Bonville
C A
CA
Rosenberg
H F
HF
D000234:Adenoids; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology / Q000821:virology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D015726:Giant Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D005912:Gliotoxin / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007633:Keratins / Q000096:biosynthesis / Q000235:genetics*; D007822:Laryngeal Neoplasms; D016328:NF-kappa B / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis; D012136:Respiratory Syncytial Viruses / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
D016328:NF-kappa B; D011994:Recombinant Proteins; D005912:Gliotoxin; D007633:Keratins