Cell Cycle Arrest by Transforming Growth Factor 1 Enhances Replication of Respiratory Syncytial Virus in Lung Epithelial Cells
| Autor: | Farhad Imani, Douglas M. Ornoff, Jennifer Y. Zeng, John D. Gibbs, Heather A. Igo |
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| Rok vydání: | 2009 |
| Předmět: |
Cell cycle checkpoint
viruses Immunology Respiratory Mucosa Biology Microbiology Virus Cell Line Transforming Growth Factor beta1 Virology Humans Autocrine signalling Child Cells Cultured Cell growth Cell Cycle Epithelial Cells Cell cycle respiratory system Virus-Cell Interactions Viral replication Cell culture Insect Science Child Preschool Respiratory Syncytial Virus Human Transforming growth factor |
| Zdroj: | Journal of Virology |
| ISSN: | 0022-538X |
| DOI: | 10.1128/jvi.00806-09 |
| Popis: | Respiratory syncytial virus (RSV) is a common respiratory viral infection in children which is associated with immune dysregulation and subsequent induction and exacerbations of asthma. We recently reported that treatment of primary human epithelial cells (PHBE cells) with transforming growth factor β (TGF-β) enhanced RSV replication. Here, we report that the enhancement of RSV replication is mediated by induction of cell cycle arrest. These data were confirmed by using pharmacologic inhibitors of cell cycle progression, which significantly enhanced RSV replication. Our data also showed that RSV infection alone resulted in cell cycle arrest in A549 and PHBE cells. Interestingly, our data showed that RSV infection induced the expression of TGF-β in epithelial cells. Blocking of TGF-β with anti-TGF-β antibody or use of a specific TGF-β receptor signaling inhibitor resulted in rescue of the RSV-induced cell cycle arrest, suggesting an autocrine mechanism. Collectively, our data demonstrate that RSV regulates the cell cycle through TGF-β in order to enhance its replication. These findings identify a novel pathway for upregulation of virus replication and suggest a plausible mechanism for association of RSV with immune dysregulation and asthma. |
| Databáze: | OpenAIRE |
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