Epstein-Barr virus replication within pulmonary epithelial cells in cryptogenic fibrosing alveolitis.

Abstract

Background -Cryptogenic fibrosing alveolitis (synonymous with idiopathic pulmonary fibrosis) is a clinically heterogeneous condition in which the precipitating factor is unclear. Both environmental and infective factors have been implicated. An association between Epstein-Barr virus (EBV) and cryptogenic fibrosing alveolitis was suggested over a decade ago by a study based on EBV serology, but the significance of this has been unclear. Methods -Lung tissue obtained surgically from patients (n = 20) with cryptogenic fibrosing alveolitis was investigated for evidence ofEBV replication and compared with lung tissue from 21 control patients. Fourteen ofthe 20 patients had received no specific therapy for cryptogenic fibrosing alveolitis at the time ofbiopsy. Monoclonal antibodies directed against the EBV viral antigens, EBV viral capsid antigen (VCA) and gp 3401220 antigen, which are ex-

Inhibition of NF-κB Signaling Reduces Virus Load and Gammaherpesvirus-Induced Pulmonary Fibrosis

“…Specifically, Epstein-Barr virus (EBV) DNA and protein have been detected in 40 to 70% of lung tissue of IPF patients, compared with 10 to 17% of lung controls. [2][3][4][5][6][7] Our group has detected viral DNA for EBV, Kaposi's sarcoma-associated herpesvirus (KSHV), and Cytomegalovirus herpesvirus in Ͼ95% of lung samples of IPF patients, with statically higher frequency compared with patients with non-IPF lung diseases. 5 We have developed a model of chronic herpesvirusinduced pulmonary fibrosis infection using the herpesvirus murine gammaherpesvirus 68 (MHV68), a natural pathogen of wild murid rodents that has strong genetic and biological similarities with the human gammaherpesviruses EBV and KSHV.…”

Chronic interstitial lung disease due to Epstein-Barr virus infection in two infants

“…There was no difference in EBV detection when comparing patients with, to those without, immunosuppressive therapy [5]. A later report, including 12 patients with IPF, two with IPF and associated systemic sclerosis, 10 with other pulmonary disorders and three healthy control subjects remained unable to confirm this finding; IHC showed inconsistent focal positive staining with anti-EBV antibodies, but there was neither evidence of EBV-RNA using in situ hybridization nor traces of EBV-DNA following gene amplification [6].…”

“…Using monoclonal antibodies against viral antigen, EBV replication within type II alveolar cells was shown to occur in adult cryptogenic fibrosing alveolitis (CFA; idiopathic pulmonary fibrosis, IPF) [5]. As these cells may have a critical role in the deposition of type I collagen in the lung, a direct relationship between viral injury and CFA was suggested [5].…”

“…Using monoclonal antibodies against viral antigen, EBV replication within type II alveolar cells was shown to occur in adult cryptogenic fibrosing alveolitis (CFA; idiopathic pulmonary fibrosis, IPF) [5]. As these cells may have a critical role in the deposition of type I collagen in the lung, a direct relationship between viral injury and CFA was suggested [5]. A different study, using immunohistochemistry (IHC), in situ hybridization and polymerase chain reaction (PCR) analysis on lung biopsy samples from patients with CFA did not support this hypothesis [6].…”

Viruses: Cofactors in Idiopathic Pulmonary Fibrosis

“…However, in other group, comprised of interstitial lung disease (ILD) of known cause, the EBV serological profiles were normal [18]. While previous study only proposed the association of EBV to IPF, Egan et al [19] reported replicating EBV within type II alveolar cells of the lower respiratory tract in IPF patients. Furthermore, the authors proposed that EBV may be an immune trigger therefore potentially offering a novel opportunity for treatment of IPF by anti-viral therapy.…”