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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Jul 15;89(14):6560–6564. doi: 10.1073/pnas.89.14.6560

Coinfection with multiple strains of the Epstein-Barr virus in human immunodeficiency virus-associated hairy leukoplakia.

D M Walling 1, S N Edmiston 1, J W Sixbey 1, M Abdel-Hamid 1, L Resnick 1, N Raab-Traub 1
PMCID: PMC49541  PMID: 1321443

Abstract

Epstein-Barr virus DNA was analyzed from specimens of hairy leukoplakia, an oral lesion that occurs in patients infected with the human immunodeficiency virus. The simultaneous presence of both type 1 and type 2 Epstein-Barr virus was demonstrated by Southern blot analysis and polymerase chain reaction assay. Restriction fragment length polymorphisms in the BamHI WYH region and in clones of the EcoRI C region suggested the presence of multiple strains of type 1 and type 2 viruses. The demonstration of multiple variably sized BamHI H fragments on Southern blot analysis and cloning of the EBNA-2 gene coding region also suggested the presence of multiple viral strains or variants coinfecting hairy leukoplakia. Recombination of the viral genome in and around the EBNA-2 gene apparently generated viral variants that replicated efficiently, one of which appeared to increase in abundance in a lesion over time. These data indicate that hairy leukoplakia involves coinfection with multiple strains of replicating Epstein-Barr virus and the endogenous generation of viral variants, some of which have mutations of the EBNA-2 gene.

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Selected References

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  1. Cen H., Breinig M. C., Atchison R. W., Ho M., McKnight J. L. Epstein-Barr virus transmission via the donor organs in solid organ transplantation: polymerase chain reaction and restriction fragment length polymorphism analysis of IR2, IR3, and IR4. J Virol. 1991 Feb;65(2):976–980. doi: 10.1128/jvi.65.2.976-980.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cohen J. I., Wang F., Kieff E. Epstein-Barr virus nuclear protein 2 mutations define essential domains for transformation and transactivation. J Virol. 1991 May;65(5):2545–2554. doi: 10.1128/jvi.65.5.2545-2554.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Countryman J., Miller G. Activation of expression of latent Epstein-Barr herpesvirus after gene transfer with a small cloned subfragment of heterogeneous viral DNA. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4085–4089. doi: 10.1073/pnas.82.12.4085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dambaugh T., Beisel C., Hummel M., King W., Fennewald S., Cheung A., Heller M., Raab-Traub N., Kieff E. Epstein-Barr virus (B95-8) DNA VII: molecular cloning and detailed mapping. Proc Natl Acad Sci U S A. 1980 May;77(5):2999–3003. doi: 10.1073/pnas.77.5.2999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dambaugh T., Hennessy K., Chamnankit L., Kieff E. U2 region of Epstein-Barr virus DNA may encode Epstein-Barr nuclear antigen 2. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7632–7636. doi: 10.1073/pnas.81.23.7632. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Heller M., Dambaugh T., Kieff E. Epstein-Barr virus DNA. IX. Variation among viral DNAs from producer and nonproducer infected cells. J Virol. 1981 May;38(2):632–648. doi: 10.1128/jvi.38.2.632-648.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Katz B. Z., Andiman W. A., Eastman R., Martin K., Miller G. Infection with two genotypes of Epstein-Barr virus in an infant with AIDS and lymphoma of the central nervous system. J Infect Dis. 1986 Mar;153(3):601–604. doi: 10.1093/infdis/153.3.601. [DOI] [PubMed] [Google Scholar]
  10. Katz B. Z., Niederman J. C., Olson B. A., Miller G. Fragment length polymorphisms among independent isolates of Epstein-Barr virus from immunocompromised and normal hosts. J Infect Dis. 1988 Feb;157(2):299–308. doi: 10.1093/infdis/157.2.299. [DOI] [PubMed] [Google Scholar]
  11. Lin J. C., Raab-Traub N. Two strains of Epstein-Barr virus (B95-8 and a P3HR-1 subclone) that lack defective genomes induce early antigen and cause abortive infection of Raji cells. J Virol. 1987 Jun;61(6):1985–1991. doi: 10.1128/jvi.61.6.1985-1991.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Little P. F., Cross S. H. A cosmid vector that facilitates restriction enzyme mapping. Proc Natl Acad Sci U S A. 1985 May;82(10):3159–3163. doi: 10.1073/pnas.82.10.3159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lung M. L., Chang R. S., Jones J. H. Genetic polymorphism of natural Epstein-Barr virus isolates from infectious mononucleosis patients and healthy carriers. J Virol. 1988 Oct;62(10):3862–3866. doi: 10.1128/jvi.62.10.3862-3866.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Miller G., Robinson J., Heston L., Lipman M. Differences between laboratory strains of Epstein-Barr virus based on immortalization, abortive infection, and interference. Proc Natl Acad Sci U S A. 1974 Oct;71(10):4006–4010. doi: 10.1073/pnas.71.10.4006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Niedobitek G., Young L. S., Lau R., Brooks L., Greenspan D., Greenspan J. S., Rickinson A. B. 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. doi: 10.1099/0022-1317-72-12-3035. [DOI] [PubMed] [Google Scholar]
  16. Patton D. F., Shirley P., Raab-Traub N., Resnick L., Sixbey J. W. Defective viral DNA in Epstein-Barr virus-associated oral hairy leukoplakia. J Virol. 1990 Jan;64(1):397–400. doi: 10.1128/jvi.64.1.397-400.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Raab-Traub N., Dambaugh T., Kieff E. DNA of Epstein-Barr virus VIII: B95-8, the previous prototype, is an unusual deletion derivative. Cell. 1980 Nov;22(1 Pt 1):257–267. doi: 10.1016/0092-8674(80)90173-7. [DOI] [PubMed] [Google Scholar]
  18. Raab-Traub N., Flynn K., Pearson G., Huang A., Levine P., Lanier A., Pagano J. The differentiated form of nasopharyngeal carcinoma contains Epstein-Barr virus DNA. Int J Cancer. 1987 Jan 15;39(1):25–29. doi: 10.1002/ijc.2910390106. [DOI] [PubMed] [Google Scholar]
  19. Raab-Traub N., Flynn K. The structure of the termini of the Epstein-Barr virus as a marker of clonal cellular proliferation. Cell. 1986 Dec 26;47(6):883–889. doi: 10.1016/0092-8674(86)90803-2. [DOI] [PubMed] [Google Scholar]
  20. Rabson M., Gradoville L., Heston L., Miller G. Non-immortalizing P3J-HR-1 Epstein-Barr virus: a deletion mutant of its transforming parent, Jijoye. J Virol. 1982 Dec;44(3):834–844. doi: 10.1128/jvi.44.3.834-844.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Resnick L., Herbst J. S., Ablashi D. V., Atherton S., Frank B., Rosen L., Horwitz S. N. Regression of oral hairy leukoplakia after orally administered acyclovir therapy. JAMA. 1988 Jan 15;259(3):384–388. [PubMed] [Google Scholar]
  22. Sample J., Young L., Martin B., Chatman T., Kieff E., Rickinson A., Kieff E. Epstein-Barr virus types 1 and 2 differ in their EBNA-3A, EBNA-3B, and EBNA-3C genes. J Virol. 1990 Sep;64(9):4084–4092. doi: 10.1128/jvi.64.9.4084-4092.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sculley T. B., Apolloni A., Hurren L., Moss D. J., Cooper D. A. Coinfection with A- and B-type Epstein-Barr virus in human immunodeficiency virus-positive subjects. J Infect Dis. 1990 Sep;162(3):643–648. doi: 10.1093/infdis/162.3.642. [DOI] [PubMed] [Google Scholar]
  24. Sixbey J. W., Nedrud J. G., Raab-Traub N., Hanes R. A., Pagano J. S. Epstein-Barr virus replication in oropharyngeal epithelial cells. N Engl J Med. 1984 May 10;310(19):1225–1230. doi: 10.1056/NEJM198405103101905. [DOI] [PubMed] [Google Scholar]
  25. Sixbey J. W., Shirley P., Chesney P. J., Buntin D. M., Resnick L. Detection of a second widespread strain of Epstein-Barr virus. Lancet. 1989 Sep 30;2(8666):761–765. doi: 10.1016/s0140-6736(89)90829-5. [DOI] [PubMed] [Google Scholar]
  26. Sixbey J. W., Shirley P., Sloas M., Raab-Traub N., Israele V. A transformation-incompetent, nuclear antigen 2-deleted Epstein-Barr virus associated with replicative infection. J Infect Dis. 1991 May;163(5):1008–1015. doi: 10.1093/infdis/163.5.1008. [DOI] [PubMed] [Google Scholar]
  27. Yao Q. Y., Rickinson A. B., Epstein M. A. A re-examination of the Epstein-Barr virus carrier state in healthy seropositive individuals. Int J Cancer. 1985 Jan 15;35(1):35–42. doi: 10.1002/ijc.2910350107. [DOI] [PubMed] [Google Scholar]
  28. Yao Q. Y., Rowe M., Martin B., Young L. S., Rickinson A. B. The Epstein-Barr virus carrier state: dominance of a single growth-transforming isolate in the blood and in the oropharynx of healthy virus carriers. J Gen Virol. 1991 Jul;72(Pt 7):1579–1590. doi: 10.1099/0022-1317-72-7-1579. [DOI] [PubMed] [Google Scholar]
  29. Young L. S., Dawson C. W., Clark D., Rupani H., Busson P., Tursz T., Johnson A., Rickinson A. B. Epstein-Barr virus gene expression in nasopharyngeal carcinoma. J Gen Virol. 1988 May;69(Pt 5):1051–1065. doi: 10.1099/0022-1317-69-5-1051. [DOI] [PubMed] [Google Scholar]
  30. Zimber U., Adldinger H. K., Lenoir G. M., Vuillaume M., Knebel-Doeberitz M. V., Laux G., Desgranges C., Wittmann P., Freese U. K., Schneider U. Geographical prevalence of two types of Epstein-Barr virus. Virology. 1986 Oct 15;154(1):56–66. doi: 10.1016/0042-6822(86)90429-0. [DOI] [PubMed] [Google Scholar]

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