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. 2003 Jun;41(6):2633-40.
doi: 10.1128/JCM.41.6.2633-2640.2003.

Herpesvirus DNA is consistently detected in lungs of patients with idiopathic pulmonary fibrosis

Yi-Wei Tang  1 , Joyce E Johnson, Philip J Browning, Roberto A Cruz-Gervis, Angela Davis, Barney S Graham, Kenneth L Brigham, John A Oates Jr, James E Loyd, Arlene A Stecenko
Affiliations

Herpesvirus DNA is consistently detected in lungs of patients with idiopathic pulmonary fibrosis

Yi-Wei Tang et al. J Clin Microbiol. 2003 Jun.

Abstract

On the basis of earlier reports associating Epstein-Barr Virus (EBV) with half of the cases of idiopathic pulmonary fibrosis (IPF), we hypothesized that chronic infection with EBV or a closely related herpesvirus would be detected in all cases of IPF. We tested lung specimens from 33 IPF patients (8 patients with familial IPF and 25 patients with sporadic IPF) and 25 patients with other diseases as controls for the presence of eight herpesviruses using PCR-based techniques. One or more of four herpesviruses (cytomegalovirus [CMV], EBV, human herpesvirus 7 [HHV-7], and HHV-8) were detected in 32 of 33 (97%) subjects with IPF and in 9 of 25 (36%) controls (P < 0.0001). CMV, EBV, and HHV-8 were found more frequently in IPF patients than in controls (P < 0.05, P < 0.001, and P < 0.01 respectively). Two or more herpesviruses were detected in 19 of 33 (57%) IPF patients and in 2 of 25 (8%) controls (P < 0.001). Two or more herpesviruses and HHV-8 were found more frequently in patients with sporadic IPF than in patients with familial IPF (P < 0.05 for both comparisons), and CMV was found less frequently in patients with sporadic IPF than in patients with familial IPF (P < 0.05). Immunohistochemistry for EBV or HHV-8 antigen showed viral antigen primarily in airway epithelial cells. These data support the concept that a herpesvirus could be a source of chronic antigenic stimulation in IPF.

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Figures

FIG. 1.
FIG. 1.
Percentage of lung samples from 33 patients with IPF and 25 controls with other diseases positive for herpesviruses (HVs) by PCR.
FIG. 2.
FIG. 2.
Percentage of lung samples from 25 patients with sporadic IPF (s-IPF) and 8 patients with familial IPF (f-IPF) positive for herpesviruses (HVs) by PCR.
FIG. 3.
FIG. 3.
Immunohistochemical staining of lung samples from two IPF patients for HHV-8. (A) The epithelium of all airspaces in a densely fibrotic area from sporadic IPF patient 8 marks uniformly for HHV-8 k-cyclin protein. Magnification, ×62.5. (B) Epithelial cells of a larger bronchiole from sporadic IPF patient 1 are positive for HHV-8. Magnification, ×250. (C) Endothelial cells and scattered subendothelial intimal cells from sporadic IPF patient 1 express HHV-8 k-cyclin protein. Magnification, ×250. (D) Low-power view of control tissue (normal parenchyma adjacent to a carcinoma) from control patient 11 is uniformly negative for HHV-8 cyclin. Magnification, ×62.5.
FIG. 4.
FIG. 4.
Immunohistochemical staining of lung tissue from case patient 2 showing airway epithelial cells in a small bronchiole staining positive for EBV latent membrane protein.
FIG. 5.
FIG. 5.
Serial pulmonary function testing (forced vital capacity [FVC]) in case patient 2 before and after the start of valacyclovir therapy.
See this image and copyright information in PMC

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