PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of thoraxThoraxVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
 
Thorax. 1995 December; 50(12): 1234–1239.
PMCID: PMC1021343

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 of EBV replication and compared with lung tissue from 21 control patients. Fourteen of the 20 patients had received no specific therapy for cryptogenic fibrosing alveolitis at the time of biopsy. Monoclonal antibodies directed against the EBV viral antigens, EBV viral capsid antigen (VCA) and gp 340/220 antigen, which are expressed during the lytic phase of the EBV life cycle, were studied. RESULTS--Fourteen (70%) of the 20 patients with cryptogenic fibrosing alveolitis were positive for both EBV VCA and gp 340/220 compared with two (9%) of the 21 controls. In the patients with cryptogenic fibrosing alveolitis viral replication was localised to pulmonary epithelial cells using epithelial cell markers, and immunohistochemical analysis confirmed the staining to be within type II alveolar cells. CONCLUSIONS--This is the first report of in vivo EBV replication within epithelial cells of the lower respiratory tract in an immunocompetent human host. Furthermore, this suggests that EBV may be an immune trigger or contribute to lung injury in cryptogenic fibrosing alveolitis, thus offering a potential new avenue of treatment.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Johnston I, Britton J, Kinnear W, Logan R. Rising mortality from cryptogenic fibrosing alveolitis. BMJ. 1990 Nov 3;301(6759):1017–1021. [PMC free article] [PubMed]
  • Billings CG, Howard P. Hypothesis: exposure to solvents may cause fibrosing alveolitis. Eur Respir J. 1994 Jun;7(6):1172–1176. [PubMed]
  • Vergnon JM, Vincent M, de Thé G, Mornex JF, Weynants P, Brune J. Cryptogenic fibrosing alveolitis and Epstein-Barr virus: an association? Lancet. 1984 Oct 6;2(8406):768–771. [PubMed]
  • Niedobitek G, Young LS. Epstein-Barr virus persistence and virus-associated tumours. Lancet. 1994 Feb 5;343(8893):333–335. [PubMed]
  • Lung ML, Lam WK, So SY, Lam WP, Chan KH, Ng MH. Evidence that respiratory tract is major reservoir for Epstein-Barr virus. Lancet. 1985 Apr 20;1(8434):889–892. [PubMed]
  • Ashcroft T, Simpson JM, Timbrell V. Simple method of estimating severity of pulmonary fibrosis on a numerical scale. J Clin Pathol. 1988 Apr;41(4):467–470. [PMC free article] [PubMed]
  • Stewart JP, Arrand JR. Expression of the Epstein-Barr virus latent membrane protein in nasopharyngeal carcinoma biopsy specimens. Hum Pathol. 1993 Mar;24(3):239–242. [PubMed]
  • Stewart JP, Hampson IN, Heinrich HW, Mackett M, Arrand JR. Enhanced expression of the Epstein-Barr virus latent membrane protein by a recombinant vaccinia virus. J Gen Virol. 1989 May;70(Pt 5):1231–1237. [PubMed]
  • Hoffman GJ, Lazarowitz SG, Hayward SD. Monoclonal antibody against a 250,000-dalton glycoprotein of Epstein-Barr virus identifies a membrane antigen and a neutralizing antigen. Proc Natl Acad Sci U S A. 1980 May;77(5):2979–2983. [PubMed]
  • Holmes GP, Kaplan JE, Stewart JA, Hunt B, Pinsky PF, Schonberger LB. A cluster of patients with a chronic mononucleosis-like syndrome. Is Epstein-Barr virus the cause? JAMA. 1987 May 1;257(17):2297–2302. [PubMed]
  • Henle W, Henle G. Epstein-Barr virus-specific serology in immunologically compromised individuals. Cancer Res. 1981 Nov;41(11 Pt 1):4222–4225. [PubMed]
  • Jimenez SA. New insights into the pathogenesis of interstitial pulmonary fibrosis. Thorax. 1994 Mar;49(3):193–195. [PMC free article] [PubMed]
  • Howe JG, Steitz JA. Localization of Epstein-Barr virus-encoded small RNAs by in situ hybridization. Proc Natl Acad Sci U S A. 1986 Dec;83(23):9006–9010. [PubMed]
  • MacMahon EM, Glass JD, Hayward SD, Mann RB, Becker PS, Charache P, McArthur JC, Ambinder RF. Epstein-Barr virus in AIDS-related primary central nervous system lymphoma. Lancet. 1991 Oct 19;338(8773):969–973. [PubMed]
  • Clemens MJ. The small RNAs of Epstein-Barr virus. Mol Biol Rep. 1993 Feb;17(2):81–92. [PubMed]
  • Hoffmann DG, Gedebou M, Jimenez A, Nichols WS, Marchevsky A. Detection of Epstein-Barr virus by polymerase chain reaction in transbronchial biopsies of lung transplant recipients: evidence of infection? Mod Pathol. 1993 Sep;6(5):555–559. [PubMed]
  • Sixbey JW, Nedrud JG, Raab-Traub N, Hanes RA, Pagano JS. Epstein-Barr virus replication in oropharyngeal epithelial cells. N Engl J Med. 1984 May 10;310(19):1225–1230. [PubMed]
  • Niedobitek G, Young LS, Lau R, Brooks L, Greenspan D, Greenspan JS, Rickinson AB. Epstein-Barr virus infection in oral hairy leukoplakia: virus replication in the absence of a detectable latent phase. J Gen Virol. 1991 Dec;72(Pt 12):3035–3046. [PubMed]
  • Revoltella RP, Vigneti E, Fruscalzo A, Park M, Ragona G, Rocchi G, Calef E. Epstein-Barr virus DNA sequences in precursor monocyte-macrophage cell lines established from the bone marrow of children with maturation defects of haematopoiesis. J Gen Virol. 1989 May;70(Pt 5):1203–1215. [PubMed]
  • Gosselin J, Menezes J, D'Addario M, Hiscott J, Flamand L, Lamoureux G, Oth D. Inhibition of tumor necrosis factor-alpha transcription by Epstein-Barr virus. Eur J Immunol. 1991 Jan;21(1):203–208. [PubMed]
  • Sunil-Chandra NP, Efstathiou S, Arno J, Nash AA. Virological and pathological features of mice infected with murine gamma-herpesvirus 68. J Gen Virol. 1992 Sep;73(Pt 9):2347–2356. [PubMed]
  • Millar AB, Patou G, Miller RF, Grundy JE, Katz DR, Weller IV, Semple SJ. Cytomegalovirus in the lungs of patients with AIDS. Respiratory pathogen or passenger? Am Rev Respir Dis. 1990 Jun;141(6):1474–1477. [PubMed]
  • Carrigan DR, Drobyski WR, Russler SK, Tapper MA, Knox KK, Ash RC. Interstitial pneumonitis associated with human herpesvirus-6 infection after marrow transplantation. Lancet. 1991 Jul 20;338(8760):147–149. [PubMed]
  • Fujinami RS, Nelson JA, Walker L, Oldstone MB. Sequence homology and immunologic cross-reactivity of human cytomegalovirus with HLA-DR beta chain: a means for graft rejection and immunosuppression. J Virol. 1988 Jan;62(1):100–105. [PMC free article] [PubMed]
  • Horan MA. Immunosenescence and mucosal immunity. Lancet. 1993 Mar 27;341(8848):793–794. [PubMed]
  • Scott J, Johnston I, Britton J. What causes cryptogenic fibrosing alveolitis? A case-control study of environmental exposure to dust. BMJ. 1990 Nov 3;301(6759):1015–1017. [PMC free article] [PubMed]
  • Matsui R, Goldstein RH, Mihal K, Brody JS, Steele MP, Fine A. Type I collagen formation in rat type II alveolar cells immortalised by viral gene products. Thorax. 1994 Mar;49(3):201–206. [PMC free article] [PubMed]

Articles from Thorax are provided here courtesy of BMJ Publishing Group