Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1995 Jul;69(7):3987–3994. doi: 10.1128/jvi.69.7.3987-3994.1995

The Epstein-Barr virus (EBV) BZLF2 gene product associates with the gH and gL homologs of EBV and carries an epitope critical to infection of B cells but not of epithelial cells.

Q Li 1, S M Turk 1, L M Hutt-Fletcher 1
PMCID: PMC189130  PMID: 7539502

Abstract

Glycoprotein gp85, the product of the BXLF2 open reading frame (ORF), is the gH homolog of Epstein-Barr virus (EBV) and has been implicated in penetration of virus into B cells. Like its counterparts in other herpesviruses, it associates with a gL homolog, gp25, which is the product of the BKRF2 ORF. Unlike the gH homologs of other herpesviruses, however, gp85 also complexes with two additional glycoproteins of 42 and 38 kDa. Glycoproteins gp42 and gp38 were determined to be alternatively processed forms of the BZLF2 gene product. Coexpression of EBV gH and gL facilitated transport of gH to the cell surface and resulted in formation of a stable complex of gH and gL. It also restored expression of an epitope recognized by monoclonal antibody E1D1, which immunoprecipitates the native gH complex but not recombinant gH expressed in isolation. Coexpression of gH, gL, and the BZLF2 ORF restored expression of an epitope recognized by a second monoclonal antibody, F-2-1, which immunoprecipitates the native gH-gL-gp42/38 complex but not the complex of recombinant gH and gL alone. The epitope recognized by antibody F-2-1 was mapped to the BZLF2 gene product itself. Antibody F-2-1 inhibited the ability of EBV to infect B lymphocytes but had no effect on the ability of the virus to infect the epithelial cell line SVK-CR2. In contrast, antibody E1D1 had no effect on infection of the B-cell line but inhibited infection of the epithelial cell line. These results indicate that penetration of the two cell types by EBV involves differential use of the gH-gL-gp42/38 complex and suggest the hypothesis that the BZLF2 gene product has evolved as a unique adaptation to infection of B lymphocytes by EBV.

Full Text

The Full Text of this article is available as a PDF (669.5 KB).

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. Cooper N. R., Bradt B. M., Rhim J. S., Nemerow G. R. CR2 complement receptor. J Invest Dermatol. 1990 Jun;94(6 Suppl):112S–117S. doi: 10.1111/1523-1747.ep12876069. [DOI] [PubMed] [Google Scholar]
  3. Forghani B., Ni L., Grose C. Neutralization epitope of the varicella-zoster virus gH:gL glycoprotein complex. Virology. 1994 Mar;199(2):458–462. doi: 10.1006/viro.1994.1145. [DOI] [PubMed] [Google Scholar]
  4. Forrester A., Farrell H., Wilkinson G., Kaye J., Davis-Poynter N., Minson T. Construction and properties of a mutant of herpes simplex virus type 1 with glycoprotein H coding sequences deleted. J Virol. 1992 Jan;66(1):341–348. doi: 10.1128/jvi.66.1.341-348.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fuller A. O., Santos R. E., Spear P. G. Neutralizing antibodies specific for glycoprotein H of herpes simplex virus permit viral attachment to cells but prevent penetration. J Virol. 1989 Aug;63(8):3435–3443. doi: 10.1128/jvi.63.8.3435-3443.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gompels U., Minson A. The properties and sequence of glycoprotein H of herpes simplex virus type 1. Virology. 1986 Sep;153(2):230–247. doi: 10.1016/0042-6822(86)90026-7. [DOI] [PubMed] [Google Scholar]
  7. Haddad R. S., Hutt-Fletcher L. M. Depletion of glycoprotein gp85 from virosomes made with Epstein-Barr virus proteins abolishes their ability to fuse with virus receptor-bearing cells. J Virol. 1989 Dec;63(12):4998–5005. doi: 10.1128/jvi.63.12.4998-5005.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Heineman T., Gong M., Sample J., Kieff E. Identification of the Epstein-Barr virus gp85 gene. J Virol. 1988 Apr;62(4):1101–1107. doi: 10.1128/jvi.62.4.1101-1107.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hutchinson L., Browne H., Wargent V., Davis-Poynter N., Primorac S., Goldsmith K., Minson A. C., Johnson D. C. A novel herpes simplex virus glycoprotein, gL, forms a complex with glycoprotein H (gH) and affects normal folding and surface expression of gH. J Virol. 1992 Apr;66(4):2240–2250. doi: 10.1128/jvi.66.4.2240-2250.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kaye J. F., Gompels U. A., Minson A. C. Glycoprotein H of human cytomegalovirus (HCMV) forms a stable complex with the HCMV UL115 gene product. J Gen Virol. 1992 Oct;73(Pt 10):2693–2698. doi: 10.1099/0022-1317-73-10-2693. [DOI] [PubMed] [Google Scholar]
  11. Li Q. X., Young L. S., Niedobitek G., Dawson C. W., Birkenbach M., Wang F., Rickinson A. B. Epstein-Barr virus infection and replication in a human epithelial cell system. Nature. 1992 Mar 26;356(6367):347–350. doi: 10.1038/356347a0. [DOI] [PubMed] [Google Scholar]
  12. Liu D. X., Gompels U. A., Nicholas J., Lelliott C. Identification and expression of the human herpesvirus 6 glycoprotein H and interaction with an accessory 40K glycoprotein. J Gen Virol. 1993 Sep;74(Pt 9):1847–1857. doi: 10.1099/0022-1317-74-9-1847. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Miller N., Hutt-Fletcher L. M. A monoclonal antibody to glycoprotein gp85 inhibits fusion but not attachment of Epstein-Barr virus. J Virol. 1988 Jul;62(7):2366–2372. doi: 10.1128/jvi.62.7.2366-2372.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Moss B., Elroy-Stein O., Mizukami T., Alexander W. A., Fuerst T. R. Product review. New mammalian expression vectors. Nature. 1990 Nov 1;348(6296):91–92. doi: 10.1038/348091a0. [DOI] [PubMed] [Google Scholar]
  16. Nemerow G. R., Mold C., Schwend V. K., Tollefson V., Cooper N. R. Identification of gp350 as the viral glycoprotein mediating attachment of Epstein-Barr virus (EBV) to the EBV/C3d receptor of B cells: sequence homology of gp350 and C3 complement fragment C3d. J Virol. 1987 May;61(5):1416–1420. doi: 10.1128/jvi.61.5.1416-1420.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Oba D. E., Hutt-Fletcher L. M. Induction of antibodies to the Epstein-Barr virus glycoprotein gp85 with a synthetic peptide corresponding to a sequence in the BXLF2 open reading frame. J Virol. 1988 Apr;62(4):1108–1114. doi: 10.1128/jvi.62.4.1108-1114.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Peeters B., de Wind N., Broer R., Gielkens A., Moormann R. Glycoprotein H of pseudorabies virus is essential for entry and cell-to-cell spread of the virus. J Virol. 1992 Jun;66(6):3888–3892. doi: 10.1128/jvi.66.6.3888-3892.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pellegrino M. A., Ferrone S., Dierich M. P., Reisfeld R. A. Enhancement of sheep red blood cell human lymphocyte rosette formation by the sulfhydryl compound 2-amino ethylisothiouronium bromide. Clin Immunol Immunopathol. 1975 Jan;3(3):324–333. doi: 10.1016/0090-1229(75)90019-7. [DOI] [PubMed] [Google Scholar]
  20. Roop C., Hutchinson L., Johnson D. C. A mutant herpes simplex virus type 1 unable to express glycoprotein L cannot enter cells, and its particles lack glycoprotein H. J Virol. 1993 Apr;67(4):2285–2297. doi: 10.1128/jvi.67.4.2285-2297.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Spaete R. R., Perot K., Scott P. I., Nelson J. A., Stinski M. F., Pachl C. Coexpression of truncated human cytomegalovirus gH with the UL115 gene product or the truncated human fibroblast growth factor receptor results in transport of gH to the cell surface. Virology. 1993 Apr;193(2):853–861. doi: 10.1006/viro.1993.1194. [DOI] [PubMed] [Google Scholar]
  22. Strnad B. C., Schuster T., Klein R., Hopkins R. F., 3rd, Witmer T., Neubauer R. H., Rabin H. Production and characterization of monoclonal antibodies against the Epstein-Barr virus membrane antigen. J Virol. 1982 Jan;41(1):258–264. doi: 10.1128/jvi.41.1.258-264.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Takada K. Cross-linking of cell surface immunoglobulins induces Epstein-Barr virus in Burkitt lymphoma lines. Int J Cancer. 1984 Jan 15;33(1):27–32. doi: 10.1002/ijc.2910330106. [DOI] [PubMed] [Google Scholar]
  24. Tanner J., Weis J., Fearon D., Whang Y., Kieff E. Epstein-Barr virus gp350/220 binding to the B lymphocyte C3d receptor mediates adsorption, capping, and endocytosis. Cell. 1987 Jul 17;50(2):203–213. doi: 10.1016/0092-8674(87)90216-9. [DOI] [PubMed] [Google Scholar]
  25. Yaswen L. R., Stephens E. B., Davenport L. C., Hutt-Fletcher L. M. Epstein-Barr virus glycoprotein gp85 associates with the BKRF2 gene product and is incompletely processed as a recombinant protein. Virology. 1993 Aug;195(2):387–396. doi: 10.1006/viro.1993.1388. [DOI] [PubMed] [Google Scholar]

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

RESOURCES