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A Rearranged Form of Epstein–Barr Virus DNA Is Associated with Idiopathic Pulmonary Fibrosis

Laboratory for Clinical and Molecular Virology, University of Edinburgh, Summerhall, Edinburgh; and North West Lung Centre and Department of Histopathology, Wythenshawe Hospital, Wythenshawe, Manchester, United Kingdom

Correspondence and requests for reprints should be addressed to Prof. James P. Stewart, Department of Medical Microbiology and Genitourinary Medicine, University of Liverpool, Duncan Building, Daulby Street, Liverpool L69 3GA, UK. E-mail: j.p.stewart{at}liv.ac.uk

An association between idiopathic pulmonary fibrosis (IPF) and productive Epstein–Barr virus (EBV) infection has been found previously. Productive EBV replication can be associated with a rearrangement in EBV genomes termed WZhet. We hypothesized that WZhet genomes might be present in patients with IPF. Thirty-nine patients with IPF, 26 lung transplant recipients, and 24 normal subjects were studied. When EBV DNA–positive lung tissue biopsies from IPF patients were analyzed, 11 of 18 (61%) were positive for WZhet. Buffy coat DNA analysis showed that 75–85% were EBV DNA–positive in both IPF and control groups. Buffy coat analysis for WZhet was positive in 16 of 27 (59%) IPF patients, compared with none of 32 lung transplant recipients and 1 of 24 (4%) normal blood donors (p 0.001). There was thus a good correlation between the presence of WZhet in lung tissue and peripheral blood. However, there was no significant association between the presence of WZhet and immunosuppressive therapy. These data further confirm the association between active EBV infection and IPF and provide a potential marker in the peripheral blood for the tracking of EBV in this disease.

Key Words: Epstein–Barr virus infections • polymerase chain reaction • pulmonary fibrosis

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