Idiopathic pulmonary fibrosis (IPF) is an increasingly common disease with a poor prognosis. Standard therapy has little or no impact in patients with advanced disease. The emerging hypothesis for the pathogenesis IPF is of repeated epithelial cell injury leading to fibrogenesis and dysregulated repair.
Herpesviruses provide a potential source of repeated epithelial cell injury. A role for viruses, especially for Epstein Barr Virus (EBV) in the pathogenesis of IPF has been suggested by serological and tissue based studies. In collaboration with Ashley Woodcock and Jim Egan (Wythenshawe Hospital, Manchester) we have previously demonstrated the presence of EBV DNA in surgical samples taken from IPF patients and localised EBV antigens to type II alveolar cells. We have also shown using MHV-68 in mice that herpesviruses can act as a cofactor in the generation of pulmonary fibrosis. Antiviral treatment can also have a beneficial effect in a proportion of IPF patients.
We are continuing to investigate the role of gammaherpeviruses in pulmonary fibrosis using our mouse model and are moving towards tranlslating our findings into the clinic.
In related work, we have shown the presence of a related equine gammaherpesvirus, equine herpesvirus 5 (EHV-5) in the lungs of horses with equine multinodular pulmonary fibrosis (EMPF). We are continuing to investigate this association as part of a Petplan Charitable Trust grant to look towards possible therapy for horses with this condition.
Relevant Group Publications
- Wilkie, G.S., Kerr, K., Stewart, J.P., Studdert, M.J. and Davison, A.J. Genome Sequences of Equid Herpesviruses 2 and 5. Genome Announcements, 3. e00119-15.doi:10.1128/genomeA.00119-15 [PDF]
- Calabrese, F., Kipar, A., Lunardi, F., Balestro, E., Perissinotto, E., Rossi, E., Nannini, N., Marulli, G., Stewart, J.P., Rea, F. (2013). Herpes virus infection is associated with vascular remodelling and pulmonary hypertension in idiopathic pulmonary fibrosis. PLoS One, 8, e55715. doi:10.1371/journal.pone.0055715 [Open Access Full Text] [PDF]
- Equine Multinodular Pulmonary Fibrosis: The Role of EHV-5 in the Pathogenesis of an Emerging Disease. (2013). Leeming, G., Kipar, A., Hartley, C., Malbon, A., Hetzel, U., and Stewart, J.P. Journal of Comparative Pathology. 148 , 74. (Abstract).[Full Text on Publisher Website] [PDF]
- West, P., Kelsall, A., Decalmer, S., Dove, W., Stewart, J.P., Bishop, P., Woodcock, A., Smith, J. (2012). PCR based bronchoscopic detection of common respiratory pathogens in chronic cough: a case control study. Cough. 8 [Open Access Full Text] [PDF]
- Soare, T., Leeming, G., Morgan, R., Papoula-Pereira, R., Kipar, A., Stewart, J.P., Hetzel, U. (2011). Equine Multinodular Pulmonary Fibrosis in the UK. Veterinary Record, 169, 313 [Full Text on Publisher Website] [PDF]
- Egan, J.J., Adamali, H.I., Lok, S.S., Stewart, J.P. and Woodcock, A.A. (2011). Ganciclovir antiviral therapy in advanced Idiopathic Pulmonary Fibrosis. Pulmonary Medicine. 2011 Article ID 240805. [Open Access Full Text] [PDF]
- Lok, S.S., Haider, Y, Howell, D., Stewart, J.P., Hasleton, P.S. and Egan, J.J. (2002). Murine gammaherpes virus a co-factor in the development of pulmonary fibrosis in bleomycin resistant mice. European Respiratory Journal. 20, 1228-1232. [Full Text on Publisher Website] [PDF]
- Kelly, B.G., Lok, S.S., Hasleton, P.S., Egan, J.J., and Stewart, J.P. (2002). A rearranged form of Epstein-Barr virus DNA is associated with idiopathic pulmonary fibrosis. American Journal of Respiratory and Critical Care Medicine. 166, 510 – 513. [Open Access Full Text] [PDF] [Supplement PDF]
- Lok, S.S., Stewart, J.P., Kelly, B.G., Hasleton, P.S., and Egan, J.J. (2001). Epstein Barr Virus and p53 in idiopathic pulmonary fibrosis. Respiratory Medicine. 95, 787-791. [Full text on Publisher Website] [PDF]
- Stewart, J.P., Egan, J.J., Ross, A.J., Kelly, B.G., Lok, S.S., Hasleton, P.S., and Woodcock, A.A. (1999). The detection of Epstein-Barr virus DNA in lung tissue from idiopathic pulmonary fibrosis patients. American Journal of Respiratory and Critical Care Medicine. 159, 1336-1341. [Open Access Full Text] [PDF]
- Egan, J.J., Woodcock, A.A. and Stewart, J.P. (1997). Viruses and idiopathic pulmonary fibrosis. European Respiratory Journal. 10, 1433-1437. (Review). [Open Access PDF] [PDF]
- Egan, J.J., Stewart, J.P., Hasleton, P.S., Yonan, N., Bishop, P., Arrand, J.R., Rahman, A.N., Carroll, K.B. and Woodcock, A.A. (1996). Epstein-Barr virus associated graft failure following heart/lung transplantation. Thorax. 51, 1160-1162. [Full Text on Publisher Website] [PDF]
- Egan, J., Stewart, J.P., Hasleton, P.S., Carroll, K.B, Arrand, J.R., and Woodcock, A.A. (1995). Epstein-Barr virus replication within pulmonary epithelial cells in cryptogenic fibrosing alveolitis. Thorax. 50, 1240-1245. [Full Text at Publisher Website] [PDF]with Editorial Comment at Hogg, J.C. (1995). Epstein-Barr virus and cryptogenic fibrosing alveolitis. Thorax 50, 1232 [PDF on Publisher Website]
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