PT  - JOURNAL ARTICLE
AU  - Andrea P. Malizia
AU  - Dermot Walls
AU  - Jim J. Egan
AU  - Peter P. Doran
TI  - Viral infection drives tissue fibrosis <em>in vitro</em>
AID  - 10.1183/09059180.00010707
DP  - 2008 Apr 01
TA  - European Respiratory Review
PG  - 49--50
VI  - 17
IP  - 107
4099  - http://err.ersjournals.com/content/17/107/49.short
4100  - http://err.ersjournals.com/content/17/107/49.full
SO  - EUROPEAN RESPIRATORY REVIEW2008 Apr 01; 17
AB  - Idiopathic Pulmonary Fibrosis (IPF) is a refractory and lethal interstitial lung disease characterized by loss of alveolar epithelial cells, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. In this study we utilised a microarray-based differential gene expression analysis strategy to identify molecular drivers of EBV associated with lung fibrosis. A549 cells and an alveolar epithelial cell line infected with EBV (VAAK) were used to identify genes whose expression was altered by EBV reactivation. EBV reactivation by TGFbeta1 drives alterations in expression of non-canonical Wnt pathway mediators, implicating it in epithelial mesenchymal transition (EMT), the molecular event underpinning scar production in tissue fibrosis. Cell invasion, EMT correlated transcripts expression, GSK-3b and c-Jun activation were altered in response to non-canonical Wnt pathway regulation. The role of EBV in promoting fibrosis can be attenuated by antiviral strategies and inhibition of Wnt signalling. Activation of non-canonical Wnt signalling pathway by EBV in epithelial cells suggests a novel mechanism of tissue fibrosis. These data present a framework for further description of the link between infectious agents and fibrosis, a significant disease burden.