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. 1986 Aug;83(15):5703–5707. doi: 10.1073/pnas.83.15.5703

Characterization of two related Epstein-Barr virus-encoded membrane proteins that are differentially expressed in Burkitt lymphoma and in vitro-transformed cell lines.

S Modrow, H Wolf
PMCID: PMC386357  PMID: 3016715

Abstract

Two related but differentially expressed potential membrane proteins of Epstein-Barr virus are encoded by the same reading frame in the EcoRI D het region of the viral genome. Potential antigenic sites in the amino acid sequence of these proteins were selected by computer-aided prediction of the secondary structure and two oligopeptides corresponding to regions located in different parts of the proteins were synthesized chemically. Rabbit antisera to these peptides were used for immunoprecipitation of the native viral proteins from Epstein-Barr virus-positive cell lines from various sources. Both predicted membrane proteins could be precipitated from cell lines that had been transformed in vitro with EBV or from cell lines derived from infectious mononucleosis patients. In cell lines established from Burkitt lymphoma, only the smaller polypeptide, which lacks 138 amino acids from the amino terminus, could be identified. Using the synthetic peptides as antigens in ELISA, we detected elevated antibody titers in sera from patients with infectious mononucleosis and nasopharyngeal carcinoma.

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Selected References

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

  1. Baer R., Bankier A. T., Biggin M. D., Deininger P. L., Farrell P. J., Gibson T. J., Hatfull G., Hudson G. S., Satchwell S. C., Séguin C. DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature. 1984 Jul 19;310(5974):207–211. doi: 10.1038/310207a0. [DOI] [PubMed] [Google Scholar]
  2. Bar R. S., DeLor C. J., Clausen K. P., Hurtubise P., Henle W., Hewetson J. F. Fatal infectious mononucleosis in a family. N Engl J Med. 1974 Feb 14;290(7):363–367. doi: 10.1056/NEJM197402142900704. [DOI] [PubMed] [Google Scholar]
  3. Chou P. Y., Fasman G. D. Prediction of protein conformation. Biochemistry. 1974 Jan 15;13(2):222–245. doi: 10.1021/bi00699a002. [DOI] [PubMed] [Google Scholar]
  4. Chou P. Y., Fasman G. D. Prediction of the secondary structure of proteins from their amino acid sequence. Adv Enzymol Relat Areas Mol Biol. 1978;47:45–148. doi: 10.1002/9780470122921.ch2. [DOI] [PubMed] [Google Scholar]
  5. Cohen G. H., Dietzschold B., Ponce de Leon M., Long D., Golub E., Varrichio A., Pereira L., Eisenberg R. J. Localization and synthesis of an antigenic determinant of herpes simplex virus glycoprotein D that stimulates the production of neutralizing antibody. J Virol. 1984 Jan;49(1):102–108. doi: 10.1128/jvi.49.1.102-108.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Emini E. A., Hughes J. V., Perlow D. S., Boger J. Induction of hepatitis A virus-neutralizing antibody by a virus-specific synthetic peptide. J Virol. 1985 Sep;55(3):836–839. doi: 10.1128/jvi.55.3.836-839.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fennewald S., van Santen V., Kieff E. Nucleotide sequence of an mRNA transcribed in latent growth-transforming virus infection indicates that it may encode a membrane protein. J Virol. 1984 Aug;51(2):411–419. doi: 10.1128/jvi.51.2.411-419.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fischer D. K., Robert M. F., Shedd D., Summers W. P., Robinson J. E., Wolak J., Stefano J. E., Miller G. Identification of Epstein-Barr nuclear antigen polypeptide in mouse and monkey cells after gene transfer with a cloned 2.9-kilobase-pair subfragment of the genome. Proc Natl Acad Sci U S A. 1984 Jan;81(1):43–47. doi: 10.1073/pnas.81.1.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Garnier J., Osguthorpe D. J., Robson B. Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins. J Mol Biol. 1978 Mar 25;120(1):97–120. doi: 10.1016/0022-2836(78)90297-8. [DOI] [PubMed] [Google Scholar]
  11. Gerper P., Whang-Peng J., Monroe J. H. Transformation and chromosome changes induced by Epstein-Barr virus in normal human leukocyte cultures. Proc Natl Acad Sci U S A. 1969 Jul;63(3):740–747. doi: 10.1073/pnas.63.3.740. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Henle G., Henle W., Clifford P., Diehl V., Kafuko G. W., Kirya B. G., Klein G., Morrow R. H., Munube G. M., Pike P. Antibodies to Epstein-Barr virus in Burkitt's lymphoma and control groups. J Natl Cancer Inst. 1969 Nov;43(5):1147–1157. [PubMed] [Google Scholar]
  13. Henle G., Henle W., Diehl V. Relation of Burkitt's tumor-associated herpes-ytpe virus to infectious mononucleosis. Proc Natl Acad Sci U S A. 1968 Jan;59(1):94–101. doi: 10.1073/pnas.59.1.94. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Henle W., Diehl V., Kohn G., Zur Hausen H., Henle G. Herpes-type virus and chromosome marker in normal leukocytes after growth with irradiated Burkitt cells. Science. 1967 Sep 1;157(3792):1064–1065. doi: 10.1126/science.157.3792.1064. [DOI] [PubMed] [Google Scholar]
  15. Henle W., Henle G., Zajac B. A., Pearson G., Waubke R., Scriba M. Differential reactivity of human serums with early antigens induced by Epstein-Barr virus. Science. 1970 Jul 10;169(3941):188–190. doi: 10.1126/science.169.3941.188. [DOI] [PubMed] [Google Scholar]
  16. Hennessy K., Fennewald S., Hummel M., Cole T., Kieff E. A membrane protein encoded by Epstein-Barr virus in latent growth-transforming infection. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7207–7211. doi: 10.1073/pnas.81.22.7207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hennessy K., Fennewald S., Kieff E. A third viral nuclear protein in lymphoblasts immortalized by Epstein-Barr virus. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5944–5948. doi: 10.1073/pnas.82.17.5944. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hennessy K., Kieff E. One of two Epstein-Barr virus nuclear antigens contains a glycine-alanine copolymer domain. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5665–5669. doi: 10.1073/pnas.80.18.5665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hopp T. P. Immunogenicity of a synthetic HBsAg peptide: enhancement by conjugation to a fatty acid carrier. Mol Immunol. 1984 Jan;21(1):13–16. doi: 10.1016/0161-5890(84)90084-1. [DOI] [PubMed] [Google Scholar]
  20. Hopp T. P., Woods K. R. Prediction of protein antigenic determinants from amino acid sequences. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3824–3828. doi: 10.1073/pnas.78.6.3824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hudson G. S., Farrell P. J., Barrell B. G. Two related but differentially expressed potential membrane proteins encoded by the EcoRI Dhet region of Epstein-Barr virus B95-8. J Virol. 1985 Feb;53(2):528–535. doi: 10.1128/jvi.53.2.528-535.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kaiser E., Colescott R. L., Bossinger C. D., Cook P. I. Color test for detection of free terminal amino groups in the solid-phase synthesis of peptides. Anal Biochem. 1970 Apr;34(2):595–598. doi: 10.1016/0003-2697(70)90146-6. [DOI] [PubMed] [Google Scholar]
  23. Klein G., Dombos L. Relationship between the sensitivity of EBV-carrying lymphoblastoid lines to superinfection and the inducibility of the resident viral genome. Int J Cancer. 1973 Mar 15;11(2):327–337. doi: 10.1002/ijc.2910110210. [DOI] [PubMed] [Google Scholar]
  24. Klein G., Giovanella B., Westman A., Stehlin J. S., Mumford D. An EBV-genome-negative cell line established from an American Burkitt lymphoma; receptor characteristics. EBV infectibility and permanent conversion into EBV-positive sublines by in vitro infection. Intervirology. 1975;5(6):319–334. doi: 10.1159/000149930. [DOI] [PubMed] [Google Scholar]
  25. Klein G., Lindahl T., Jondal M., Leibold W., Menézes J., Nilsson K., Sundström C. Continuous lymphoid cell lines with characteristics of B cells (bone-marrow-derived), lacking the Epstein-Barr virus genome and derived from three human lymphomas. Proc Natl Acad Sci U S A. 1974 Aug;71(8):3283–3286. doi: 10.1073/pnas.71.8.3283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lerner M. R., Andrews N. C., Miller G., Steitz J. A. Two small RNAs encoded by Epstein-Barr virus and complexed with protein are precipitated by antibodies from patients with systemic lupus erythematosus. Proc Natl Acad Sci U S A. 1981 Feb;78(2):805–809. doi: 10.1073/pnas.78.2.805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Liu F. T., Zinnecker M., Hamaoka T., Katz D. H. New procedures for preparation and isolation of conjugates of proteins and a synthetic copolymer of D-amino acids and immunochemical characterization of such conjugates. Biochemistry. 1979 Feb 20;18(4):690–693. doi: 10.1021/bi00571a022. [DOI] [PubMed] [Google Scholar]
  28. Mann K. P., Staunton D., Thorley-Lawson D. A. Epstein-Barr virus-encoded protein found in plasma membranes of transformed cells. J Virol. 1985 Sep;55(3):710–720. doi: 10.1128/jvi.55.3.710-720.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Menezes J., Jondal M., Leibold W., Dorval G. Epstein-Barr virus interactions with human lymphocyte subpopulations: virus adsorption, kinetics of expression of Epstein-Barr virus-associated nuclear antigen, and lymphocyte transformation. Infect Immun. 1976 Feb;13(2):303–310. doi: 10.1128/iai.13.2.303-310.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Miller G., Shope T., Lisco H., Stitt D., Lipman M. Epstein-Barr virus: transformation, cytopathic changes, and viral antigens in squirrel monkey and marmoset leukocytes. Proc Natl Acad Sci U S A. 1972 Feb;69(2):383–387. doi: 10.1073/pnas.69.2.383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Modrow S., Wolf H. Herpesvirus saimiri-induced proteins in lytically infected cells. I. Time-ordered synthesis. J Gen Virol. 1983 Jan;64(Pt 1):37–46. doi: 10.1099/0022-1317-64-1-37. [DOI] [PubMed] [Google Scholar]
  32. PULVERTAFT J. V. CYTOLOGY OF BURKITT'S TUMOUR (AFRICAN LYMPHOMA). Lancet. 1964 Feb 1;1(7327):238–240. doi: 10.1016/s0140-6736(64)92345-1. [DOI] [PubMed] [Google Scholar]
  33. Ragona G., Ernberg I., Klein G. Induction and biological characterization of the Epstein-Barr virus (EBV) carried by the Jijoye lymphoma line. Virology. 1980 Mar;101(2):553–557. doi: 10.1016/0042-6822(80)90473-0. [DOI] [PubMed] [Google Scholar]
  34. Slovin S. F., Schooley R. T., Thorley-Lawson D. A. Analysis of cellular immune response to EBV by using cloned T cell lines. J Immunol. 1983 May;130(5):2127–2132. [PubMed] [Google Scholar]
  35. Tanaka Y., Sugamura K., Hinuma Y. Heterogeneity of allogeneic restriction of human cytotoxic T cell clones specific for Epstein Barr virus. J Immunol. 1982 Mar;128(3):1241–1245. [PubMed] [Google Scholar]
  36. Trumper P. A., Epstein M. A., Giovanella B. C. Activation in vitro by BUdR of a productive EB virus infection in the epithelial cells of nasopharyngeal carcinoma. Int J Cancer. 1976 May 15;17(5):578–587. doi: 10.1002/ijc.2910170505. [DOI] [PubMed] [Google Scholar]
  37. Wallace L. E., Rickinson A. B., Rowe M., Epstein M. A. Epstein-Barr virus-specific cytotoxic T-cell clones restricted through a single HLA antigen. Nature. 1982 Jun 3;297(5865):413–415. doi: 10.1038/297413a0. [DOI] [PubMed] [Google Scholar]
  38. Wolf H., zur Hausen H., Becker V. EB viral genomes in epithelial nasopharyngeal carcinoma cells. Nat New Biol. 1973 Aug 22;244(138):245–247. doi: 10.1038/newbio244245a0. [DOI] [PubMed] [Google Scholar]
  39. de-Thé G., Geser A., Day N. E., Tukei P. M., Williams E. H., Beri D. P., Smith P. G., Dean A. G., Bronkamm G. W., Feorino P. Epidemiological evidence for causal relationship between Epstein-Barr virus and Burkitt's lymphoma from Ugandan prospective study. Nature. 1978 Aug 24;274(5673):756–761. doi: 10.1038/274756a0. [DOI] [PubMed] [Google Scholar]

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