1887

Abstract

Glycoprotein G-2 (gG-2) of herpes simplex virus type 2 (HSV-2) is cleaved to a secreted amino-terminal portion (sgG-2) and to a cell-associated carboxy-terminal portion which is further -glycosylated to constitute the mature gG-2 (mgG-2). In contrast to mgG-2, which is known to elicit a type-specific antibody response in the human host, information on the immunogenic properties of sgG-2 is lacking. Here the sgG-2 protein was purified on a heparin column and used for production of monoclonal antibodies (mAbs). Four anti-sgG-2 mAbs were mapped using a Pepscan technique and identified linear epitopes which localized to the carboxy-terminal part of the protein. One additional anti-sgG-2 mAb, recognizing a non-linear epitope, was reactive to three discrete peptide stretches where the most carboxy-terminally located stretch was constituted by the amino acids RRAL Although sgG-2 is rapidly secreted into the cell-culture medium after infection, the anti-sgG-2 mAbs identified substantial amounts of sgG-2 in the cytoplasm of HSV-2-infected cells. All of the anti-sgG-2 mAbs were HSV-2 specific showing no cross-reactivity to HSV-1 antigen or to HSV-1-infected cells. Similarly, sera from 50 HSV-2 isolation positive patients were all reactive to sgG-2 in an enzyme immunoassay whilst no reactivity was seen in 25 sera from HSV-1 isolation positive patients or in 25 serum samples from HSV-negative patients suggesting that sgG-2 is a novel antigen potentially suitable for type-discriminating serodiagnosis.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-83-1-157
2002-01-01
2019-10-23
Loading full text...

Full text loading...

/deliver/fulltext/jgv/83/1/0830157a.html?itemId=/content/journal/jgv/10.1099/0022-1317-83-1-157&mimeType=html&fmt=ahah

References

  1. Ashley, R. L., Militoni, J., Lee, F., Nahmias, A. & Corey, L. ( 1988; ). Comparison of western blot (immunoblot) and glycoprotein G-specific immunodot enzyme assay for detecting antibodies to herpes simplex virus type 1 and 2 in human sera. Journal of Clinical Microbiology 26, 662-667.
    [Google Scholar]
  2. Balachandran, N. & Hutt-Fletcher, L. M. ( 1985; ). Synthesis and processing of glycoprotein gG of herpes simplex virus type 2. Journal of Virology 54, 825-832.
    [Google Scholar]
  3. Crabb, B. S., Nagesha, H. S. & Studdert, M. J. ( 1992; ). Identification of equine herpesvirus 4 glycoprotein G: a type-specific, secreted glycoprotein. Virology 190, 143-154.[CrossRef]
    [Google Scholar]
  4. Dall’Olio, F., Malagolini, N., Campadelli-Fiume, G. & Serafini-Cessi, F. ( 1987; ). Glycosylation pattern of herpes simplex virus type 2 glycoprotein G from precursor species to the mature form. Archives of Virology 97, 237-249.[CrossRef]
    [Google Scholar]
  5. Dolan, A., Jamieson, F. E., Cunningham, C., Barnett, B. C. & McGeoch, D. J. ( 1998; ). The genome sequence of herpes simplex virus type 2. Journal of Virology 72, 2010-2021.
    [Google Scholar]
  6. Fazekas de St Groth, S. & Scheidegger, D. ( 1980; ). Production of monoclonal antibodies: strategy and tactics. Journal of Immunological Methods 35, 1-21.[CrossRef]
    [Google Scholar]
  7. Frank, R. ( 1992; ). Spot-synthesis: an easy technique for the positionally addressable, parallel chemical synthesis on a membrane support. Tetrahedron 48, 9217-9232.[CrossRef]
    [Google Scholar]
  8. Friguet, B., Chaffotte, A. F., Djavadi-Ohaniance, L. & Goldberg, M. E. ( 1985; ). Measurements of the true affinity constant in solution of antigen-antibody complexes by enzyme-linked immunosorbent assay. Journal of Immunological Methods 77, 305-319.[CrossRef]
    [Google Scholar]
  9. Gao, B. & Esnouf, M. P. ( 1996; ). Multiple interactive residues of recognition: elucidation of discontinuous epitopes with linear peptides. Journal of Immunology 157, 183-188.
    [Google Scholar]
  10. Geysen, H. M. ( 1985; ). Antigen–antibody interactions at the molecular level: adventures in peptide synthesis. Immunology Today 6, 364-369.[CrossRef]
    [Google Scholar]
  11. Harland, J. & Brown, M. ( 1988; ). Generation of a herpes simplex virus type 2 variant devoid of XbaI sites: removal of the 0·91 map coordinate site results in impaired synthesis of glycoprotein G-2. Journal of General Virology 69, 113-124.[CrossRef]
    [Google Scholar]
  12. Ho, D. W. T., Field, P. R., Sjögren-Jansson, E., Jeansson, S. & Cunningham, A. L. ( 1992; ). Indirect ELISA for the detection of HSV-2 specific IgG and IgM antibodies with glycoprotein G (gG-2). Journal of Virological Methods 36, 249-264.[CrossRef]
    [Google Scholar]
  13. Höhne, W. E., Küttner, G., Kiessig, S., Hausdorf, G., Grunow, R., Winkler, K., Wessner, H., Giessmann, E., Stigler, R., Schneider-Mergener, J., von Baehr, R. & Schomburg, D. ( 1993; ). Structural base of the interaction of a monoclonal antibody against p24 of HIV-1 with its peptide epitope. Molecular Immunology 30, 1213-1221.[CrossRef]
    [Google Scholar]
  14. Holland, T. C., Marlin, S. D., Levine, M. & Glorioso, J. ( 1983; ). Antigenic variants of herpes simplex virus selected with glycoprotein-specific monoclonal antibodies. Journal of Virology 45, 672-682.
    [Google Scholar]
  15. Isola, V. J., Eisenberg, R. J., Siebert, G. R., Heilman, C. J., Wilcox, W. C. & Cohen, G. H. ( 1989; ). Fine mapping of antigenic site II of herpes simplex virus glycoprotein D. Journal of Virology 63, 2325-2334.
    [Google Scholar]
  16. Jeansson, S. & Molin, L. ( 1974; ). On the occurrence of genital herpes simplex virus infection. Clinical and virological findings and relation to gonorrhoea. Acta Dermato-Venereologica 54, 479-485.
    [Google Scholar]
  17. Jeansson, S., Forsgren, M. & Svennerholm, B. ( 1983; ). Evaluation of solubilized herpes simplex virus membrane antigen by enzyme-linked immunosorbent assay. Journal of Clinical Microbiology 18, 1160-1166.
    [Google Scholar]
  18. Jemmerson, R. ( 1987; ). Antigenicity and native structure of globular proteins: low frequency of peptide reactive antibodies. Proceedings of the National Academy of Sciences, USA 84, 9180-9184.[CrossRef]
    [Google Scholar]
  19. Keil, G. M., Engelhardt, T., Karger, A. & Enz, M. ( 1996; ). Bovine herpesvirus 1 Us open reading frame 4 encodes a glycoproteoglycan. Journal of Virology 70, 3032-3038.
    [Google Scholar]
  20. Kimman, T. G., de Wind, N., Oei-Lie, N., Pol, J. M., Berns, A. J. & Gielkens, A. L. ( 1992; ). Contribution of single genes within the unique short region of Aujeszky’s disease virus (suid herpesvirus type 1) to virulence, pathogenesis and immunogenicity. Journal of General Virology 73, 243-251.[CrossRef]
    [Google Scholar]
  21. Korth, C., Stierli, B., Streit, P., Moser, M., Schaller, O., Fischer, R., Schulz-Schaeffer, W., Kretzschmar, H., Raeber, A., Braun, U., Ehrensperger, F., Hornemann, S., Glockshuber, R., Riek, R., Billeter, M., Wüthrich, K. & Oesch, B. ( 1997; ). Prion (PrPSc)-specific epitope defined by a monoclonal antibody. Nature 390, 74-77.[CrossRef]
    [Google Scholar]
  22. Kramer, A., Schuster, A., Reineke, U., Malin, R., Volkmer-Engert, R., Landgraf, C. & Schneider-Mergener, J. ( 1994; ). Combinatorial cellulose-bound peptide libraries: screening tools for the identification of peptides that bind ligands with predefined specificity. Methods. A Companion to Methods in Enzymology 6, 388–395.[CrossRef]
    [Google Scholar]
  23. Kwong, P. D., Wyatt, R., Robinson, J., Sweet, R. W., Sodroski, J. & Hendrickson, W. A. ( 1998; ). Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 393, 648-659.[CrossRef]
    [Google Scholar]
  24. Langenberg, A. G., Corey, L., Ashley, R. L., Leong, W. P. & Straus, S. E. ( 1999; ). A prospective study of new infections with herpes simplex virus type 1 and type 2. Chiron HSV Vaccine Study Group. New England Journal of Medicine 341, 1432-1438.[CrossRef]
    [Google Scholar]
  25. Laver, W. G., Air, G. M., Webster, R. G. & Smith-Gill, S. J. ( 1990; ). Epitopes on protein antigens: misconceptions and realities. Cell 61, 553-556.[CrossRef]
    [Google Scholar]
  26. Lee, F. K., Coleman, M., Pereira, L., Bailey, P. D., Tatsuno, M. & Nahmias, A. J. ( 1985; ). Detection of herpes simplex virus type 2-specific antibody with glycoprotein G. Journal of Clinical Microbiology 22, 641-644.
    [Google Scholar]
  27. Liljeqvist, J.-Å., Trybala, E., Svennerholm, B., Jeansson, S., Sjögren-Jansson, E. & Bergström, T. ( 1998; ). Localization of type-specific epitopes of herpes simplex virus type 2 glycoprotein G recognized by human and mouse antibodies. Journal of General Virology 79, 1215-1224.
    [Google Scholar]
  28. Liljeqvist, J.-Å., Svennerholm, B. & Bergström, T. ( 1999; ). Herpes simplex virus type 2 glycoprotein G-negative clinical isolates are generated by single frameshift mutations. Journal of Virology 73, 9796-9802.
    [Google Scholar]
  29. Lopez, C., Arvin, A. M. & Ashley, R. ( 1993; ). Immunity to herpesvirus infections in humans. In The Human Herpesviruses , pp. 397-425. Edited by B. Roizman, R. J. Whitley & C. Lopez. New York:Raven Press.
  30. McGeoch, D. J., Dolan, A., Donald, S. & Rixon, F. J. ( 1985; ). Sequence determination and genetic content of the short unique region in the genome of herpes simplex virus type 1. Journal of Molecular Biology 181, 1-13.[CrossRef]
    [Google Scholar]
  31. McGeoch, D. J., Moss, H. W. M., McNab, D. & Frame, M. C. ( 1987; ). DNA sequence and genetic content of the HindIII l region in the short unique component of the herpes simplex virus type 2 genome: identification of the gene encoding glycoprotein G, and evolutionary comparisons. Journal of General Virology 68, 19-38.[CrossRef]
    [Google Scholar]
  32. Marsden, H. S., Buckmaster, A., Palfreyman, J. W., Hope, R. G. & Minson, A. C. ( 1984; ). Characterization of the 92,000-dalton glycoprotein induced by herpes simplex virus type 2. Journal of Virology 50, 547-554.
    [Google Scholar]
  33. Marsden, H. S., MacAulay, K., Murray, J. & Smith, I. W. ( 1998; ). Identification of an immunodominant sequential epitope in glycoprotein G of herpes simplex virus type 2 that is useful for serotype-specific diagnosis. Journal of Medical Virology 56, 79-84.[CrossRef]
    [Google Scholar]
  34. Muggeridge, M. I., Roberts, S. R., Isola, V. J. & Eisenberg, R. J. (1990). Herpes simplex virus. In Immunochemistry of Viruses, II, The Basis for Serodiagnosis and Vaccines, pp. 459–481. Edited by M. H. V. Van Regenmortel & A. R. Neurath.
  35. Oladepo, D. K., Klapper, P. E. & Marsden, H. S. ( 2000; ). Peptide based enzyme-linked immunoassays for detection of anti-HSV-2 IgG in human sera. Journal of Virological Methods 87, 63-70.[CrossRef]
    [Google Scholar]
  36. Olofsson, S., Lundström, M., Marsden, H., Jeansson, S. & Vahlne, A. ( 1986; ). Characterization of a herpes simplex virus type 2-specified glycoprotein with affinity for N-acetylgalactosamine-specific lectins and its identification as g92K or gG. Journal of General Virology 67, 737-744.[CrossRef]
    [Google Scholar]
  37. Padlan, E. A., Silverton, E. W., Sheriff, S., Cohen, G. H., Smith-Gill, S. J. & Davies, D. R. ( 1989; ). Structure of an antibody-antigen complex: crystal structure of the HyHEL-10 Fab-lysozyme complex. Proceedings of the National Academy of Sciences, USA 86, 5938-5942.[CrossRef]
    [Google Scholar]
  38. Rea, T. J., Timmins, J. G., Long, G. W. & Post, L. E. ( 1985; ). Mapping and sequence of the gene for the pseudorabies virus glycoprotein which accumulates in the medium of infected cells. Journal of Virology 54, 21-29.
    [Google Scholar]
  39. Reineke, U., Sabat, R., Kramer, A., Stigler, R., Seifert, M., Michel, T., Volk, H. & Schneider-Mergener, J. ( 1995; ). Mapping protein-protein contact sites using cellulose-bound peptide scans. Molecular Diversity 1, 141-148.
    [Google Scholar]
  40. Reineke, U., Sabat, R., Volk, H. D. & Schneider-Mergener, J. ( 1998; ). Mapping of the interleukin-10/interleukin-10 receptor combining site. Protein Science 7, 951-960.
    [Google Scholar]
  41. Roizman, B., Norrild, B., Chan, C. & Pereira, L. ( 1984; ). Identification and preliminary mapping with monoclonal antibodies of a herpes simplex virus type 2 glycoprotein lacking a known type 1 counterpart. Virology 133, 242-247.[CrossRef]
    [Google Scholar]
  42. Schmid, D. S., Brown, D. R., Nisenbaum, R., Burke, R. L., Alexander, D., Ashley, R., Pellett, P. E. & Reeves, W. C. ( 1999; ). Limits in reliability of glycoprotein G-based type-specific serologic assays for herpes simplex virus types 1 and 2. Journal of Clinical Microbiology 37, 376-379.
    [Google Scholar]
  43. Sjögren-Jansson, E. & Jeansson, S. ( 1985; ). Large-scale production of monoclonal antibodies in dialysis tubing. Journal of Immunological Methods 84, 359-364.[CrossRef]
    [Google Scholar]
  44. Smith, T. J., Chase, E. S., Schmidt, T. J., Olson, N. H. & Baker, T. S. ( 1996; ). Neutralizing antibody to human rhinovirus 14 penetrates the receptor-binding canyon. Nature 383, 350-354.[CrossRef]
    [Google Scholar]
  45. Stevens, F. J. ( 1987; ). Modification of an ELISA-based procedure for affinity determination: correction necessary for use with bivalent antibody. Molecular Immunology 24, 1055-1060.[CrossRef]
    [Google Scholar]
  46. Stigler, R., Rüker, F., Katinger, D., Elliot, G., Höhne, W., Henklein, P., Ho, J. X., Keeling, K., Carter, D. C., Nugel, E., Kramer, A., Porstmann, T. & Schneider-Mergener, J. ( 1995; ). Interaction between a Fab fragment against gp41 of human immunodeficiency virus 1 and its peptide epitope: characterization using a peptide library and molecular modeling. Protein Engineering 8, 471-479.[CrossRef]
    [Google Scholar]
  47. Su, H. K. & Courtney, R. J. ( 1988; ). Inducible expression of herpes simplex virus type 2 glycoprotein gene gG-2 in a mammalian cell line. Journal of Virology 62, 3668-3674.
    [Google Scholar]
  48. Su, H. K., Eberle, R. & Courtney, R. J. ( 1987; ). Processing of the herpes simplex virus type 2 glycoprotein gG-2 results in secretion of a 34,000 M r cleavage product. Journal of Virology 61, 1735-1737.
    [Google Scholar]
  49. Su, H. K., Fetherston, J. D., Smith, M. E. & Courtney, R. J. ( 1993; ). Orientation of the cleavage site of the herpes simplex virus glycoprotein G-2. Journal of Virology 67, 2954-2959.
    [Google Scholar]
  50. Svennerholm, B., Olofsson, S., Jeansson, S., Vahlne, A. & Lycke, E. ( 1984; ). Herpes simplex virus type-selective enzyme-linked immunosorbent assay with Helix pomatia lectin-purified antigens. Journal of Clinical Microbiology 19, 235-239.
    [Google Scholar]
  51. Telford, E. A., Watson, M. S., McBride, K. & Davison, A. J. ( 1992; ). The DNA sequence of equine herpesvirus-1. Virology 189, 304-316.[CrossRef]
    [Google Scholar]
  52. Wald, A., Koutsky, L., Ashley, R. L. & Corey, L. ( 1997; ). Genital herpes in a primary care clinic. Demographic and sexual correlates of herpes simplex type 2 infections. Sexually Transmitted Diseases 24, 149-155.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-83-1-157
Loading
/content/journal/jgv/10.1099/0022-1317-83-1-157
Loading

Data & Media loading...

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error