Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1991 Jun;65(6):2868–2874. doi: 10.1128/jvi.65.6.2868-2874.1991

Differentiation-associated expression of the Epstein-Barr virus BZLF1 transactivator protein in oral hairy leukoplakia.

L S Young 1, R Lau 1, M Rowe 1, G Niedobitek 1, G Packham 1, F Shanahan 1, D T Rowe 1, D Greenspan 1, J S Greenspan 1, A B Rickinson 1, et al.
PMCID: PMC240913  PMID: 1851858

Abstract

The BZLF1 protein of Epstein-Barr virus (EBV) is a key immediate-early protein which has been shown to disrupt virus latency in EBV-infected B cells. We have generated a monoclonal antibody, BZ1, to BZLF1 which reacts in immunohistology, immunoblotting, and immunoprecipitation and which recognizes both the active, dimeric form and the inactive, monomeric form of the protein. Biopsies of oral hairy leukoplakia, an AIDS-associated lesion characterized by high-level EBV replication, were examined by immunohistochemistry using the BZ1 monoclonal antibody. A differentiation-associated pattern of BZLF1 expression was observed, BZ1 reacting with nuclei of the upper spinous layer of the lesion. This finding suggests that the BZLF1 promoter may be regulated by the degree of squamous differentiation. A comparison of in situ hybridization to EBV DNA and viral capsid antigen staining with BZ1 reactivity suggested that BZLF1 expression precedes rampant virus replication. The inability to detect EBV in the lower epithelial layers of oral hairy leukoplakia raises questions concerning the nature of EBV latency and persistence in stratified squamous epithelium.

Full text

PDF
2868

Images in this article

2870Image
on p.2870
2870Image
on p.2870
2871Image
on p.2871
2872Image
on p.2872
2873Image
on p.2873

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cordell J. L., Falini B., Erber W. N., Ghosh A. K., Abdulaziz Z., MacDonald S., Pulford K. A., Stein H., Mason D. Y. Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem. 1984 Feb;32(2):219–229. doi: 10.1177/32.2.6198355. [DOI] [PubMed] [Google Scholar]
  2. De Souza Y. G., Greenspan D., Felton J. R., Hartzog G. A., Hammer M., Greenspan J. S. Localization of Epstein-Barr virus DNA in the epithelial cells of oral hairy leukoplakia by in situ hybridization of tissue sections. N Engl J Med. 1989 Jun 8;320(23):1559–1560. doi: 10.1056/NEJM198906083202315. [DOI] [PubMed] [Google Scholar]
  3. Farrell P. J., Rowe D. T., Rooney C. M., Kouzarides T. Epstein-Barr virus BZLF1 trans-activator specifically binds to a consensus AP-1 site and is related to c-fos. EMBO J. 1989 Jan;8(1):127–132. doi: 10.1002/j.1460-2075.1989.tb03356.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Friedman-Kien A. E. Viral origin of hairy leukoplakia. Lancet. 1986 Sep 20;2(8508):694–695. doi: 10.1016/s0140-6736(86)90210-2. [DOI] [PubMed] [Google Scholar]
  5. Gilligan K., Rajadurai P., Resnick L., Raab-Traub N. Epstein-Barr virus small nuclear RNAs are not expressed in permissively infected cells in AIDS-associated leukoplakia. Proc Natl Acad Sci U S A. 1990 Nov;87(22):8790–8794. doi: 10.1073/pnas.87.22.8790. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gratama J. W., Oosterveer M. A., Zwaan F. E., Lepoutre J., Klein G., Ernberg I. Eradication of Epstein-Barr virus by allogeneic bone marrow transplantation: implications for sites of viral latency. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8693–8696. doi: 10.1073/pnas.85.22.8693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Greenspan D., Greenspan J. S., Conant M., Petersen V., Silverman S., Jr, de Souza Y. Oral "hairy" leucoplakia in male homosexuals: evidence of association with both papillomavirus and a herpes-group virus. Lancet. 1984 Oct 13;2(8407):831–834. doi: 10.1016/s0140-6736(84)90872-9. [DOI] [PubMed] [Google Scholar]
  8. Greenspan J. S., Greenspan D., Lennette E. T., Abrams D. I., Conant M. A., Petersen V., Freese U. K. Replication of Epstein-Barr virus within the epithelial cells of oral "hairy" leukoplakia, an AIDS-associated lesion. N Engl J Med. 1985 Dec 19;313(25):1564–1571. doi: 10.1056/NEJM198512193132502. [DOI] [PubMed] [Google Scholar]
  9. Kouzarides T., Packham G., Cook A., Farrell P. J. The BZLF1 protein of EBV has a coiled coil dimerisation domain without a heptad leucine repeat but with homology to the C/EBP leucine zipper. Oncogene. 1991 Feb;6(2):195–204. [PubMed] [Google Scholar]
  10. Lieberman P. M., Berk A. J. In vitro transcriptional activation, dimerization, and DNA-binding specificity of the Epstein-Barr virus Zta protein. J Virol. 1990 Jun;64(6):2560–2568. doi: 10.1128/jvi.64.6.2560-2568.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Löning T., Henke R. P., Reichart P., Becker J. In situ hybridization to detect Epstein-Barr virus DNA in oral tissues of HIV-infected patients. Virchows Arch A Pathol Anat Histopathol. 1987;412(2):127–133. doi: 10.1007/BF00716184. [DOI] [PubMed] [Google Scholar]
  12. Miller G. The switch between latency and replication of Epstein-Barr virus. J Infect Dis. 1990 May;161(5):833–844. doi: 10.1093/infdis/161.5.833. [DOI] [PubMed] [Google Scholar]
  13. Niedobitek G., Hamilton-Dutoit S., Herbst H., Finn T., Vetner M., Pallesen G., Stein H. Identification of Epstein-Barr virus-infected cells in tonsils of acute infectious mononucleosis by in situ hybridization. Hum Pathol. 1989 Aug;20(8):796–799. doi: 10.1016/0046-8177(89)90075-0. [DOI] [PubMed] [Google Scholar]
  14. Polack A., Hartl G., Zimber U., Freese U. K., Laux G., Takaki K., Hohn B., Gissmann L., Bornkamm G. W. A complete set of overlapping cosmid clones of M-ABA virus derived from nasopharyngeal carcinoma and its similarity to other Epstein-Barr virus isolates. Gene. 1984 Mar;27(3):279–288. doi: 10.1016/0378-1119(84)90072-6. [DOI] [PubMed] [Google Scholar]
  15. Rooney C. M., Rowe D. T., Ragot T., Farrell P. J. The spliced BZLF1 gene of Epstein-Barr virus (EBV) transactivates an early EBV promoter and induces the virus productive cycle. J Virol. 1989 Jul;63(7):3109–3116. doi: 10.1128/jvi.63.7.3109-3116.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Rooney C., Taylor N., Countryman J., Jenson H., Kolman J., Miller G. Genome rearrangements activate the Epstein-Barr virus gene whose product disrupts latency. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9801–9805. doi: 10.1073/pnas.85.24.9801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rowe M., Evans H. S., Young L. S., Hennessy K., Kieff E., Rickinson A. B. Monoclonal antibodies to the latent membrane protein of Epstein-Barr virus reveal heterogeneity of the protein and inducible expression in virus-transformed cells. J Gen Virol. 1987 Jun;68(Pt 6):1575–1586. doi: 10.1099/0022-1317-68-6-1575. [DOI] [PubMed] [Google Scholar]
  18. Rowe M., Young L. S., Cadwallader K., Petti L., Kieff E., Rickinson A. B. Distinction between Epstein-Barr virus type A (EBNA 2A) and type B (EBNA 2B) isolates extends to the EBNA 3 family of nuclear proteins. J Virol. 1989 Mar;63(3):1031–1039. doi: 10.1128/jvi.63.3.1031-1039.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Yao Q. Y., Ogan P., Rowe M., Wood M., Rickinson A. B. Epstein-Barr virus-infected B cells persist in the circulation of acyclovir-treated virus carriers. Int J Cancer. 1989 Jan 15;43(1):67–71. doi: 10.1002/ijc.2910430115. [DOI] [PubMed] [Google Scholar]
  20. Young L. S., Sixbey J. W. Epstein-Barr virus and epithelial cells: a possible role for the virus in the development of cervical carcinoma. Cancer Surv. 1988;7(3):507–518. [PubMed] [Google Scholar]
  21. Young L., Alfieri C., Hennessy K., Evans H., O'Hara C., Anderson K. C., Ritz J., Shapiro R. S., Rickinson A., Kieff E. Expression of Epstein-Barr virus transformation-associated genes in tissues of patients with EBV lymphoproliferative disease. N Engl J Med. 1989 Oct 19;321(16):1080–1085. doi: 10.1056/NEJM198910193211604. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES