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Journal of Virology, March 2007, p. 2880-2886, Vol. 81, No. 6
0022-538X/07/$08.00+0     doi:10.1128/JVI.02583-06

Transforming Growth Factor ß Enhances Respiratory Syncytial Virus Replication and Tumor Necrosis Factor Alpha Induction in Human Epithelial Cells{triangledown}

Kelly L. McCann and Farhad Imani*

Laboratory of Respiratory Biology, National Institutes of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709

Received 22 November 2006/ Accepted 20 December 2006

Asthma is characterized as a chronic inflammatory disease associated with significant tissue remodeling. Patients with asthma are more susceptible to virus-induced exacerbation, which subsequently can lead to increased rates of hospitalization and mortality. While the most common cause of asthma-related deaths is respiratory viral infections, the underlying factors in the lung environment which render asthmatic subjects more susceptible to viral exacerbation are not yet identified. Since transforming growth factor ß (TGF-ß) is a critical cytokine for lung tissue remodeling and asthma phenotype, we have focused on the effects of TGF-ß on viral replication and virus-induced inflammation. Treatment of human epithelial cells with TGF-ß increased respiratory syncytial virus (RSV) replication by approximately fourfold. Tumor necrosis factor alpha (TNF-{alpha}) mRNA and protein expression were also significantly increased above levels with RSV infection alone. The increase in RSV replication and TNF-{alpha} expression after TGF-ß treatment was concomitant with an increase in virus-induced p38 mitogen-activated protein kinase activation. Our data reveal a novel effect for TGF-ß on RSV replication and provide a potential mechanism for the exaggerated inflammatory response observed in asthmatic subjects during respiratory viral infections.

* Corresponding author. Mailing address: NIH/NIEHS, MD 2-01, 111 T.W. Alexander Dr., Research Triangle Park, NC 27709. Phone: (919) 541-5058. Fax: (919) 541-4133. E-mail: imani{at}niehs.nih.gov.

{triangledown} Published ahead of print on 3 January 2007.

Journal of Virology, March 2007, p. 2880-2886, Vol. 81, No. 6
0022-538X/07/$08.00+0     doi:10.1128/JVI.02583-06






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