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
2024-12-13
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
    [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
    [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
    [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
    [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
    [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
    [Google Scholar]
  11. Harland J., Brown M. 1988; Generation of a herpes simplex virus type 2 variant devoid of Xba I sites: removal of the 0·91 map coordinate site results in impaired synthesis of glycoprotein G-2. Journal of General Virology 69:113–124
    [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
    [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
    [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
    [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
    [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
    [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
    [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
    [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
    [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
    [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 Roizman B., Whitley R. J., Lopez C. New York: Raven Press;
    [Google Scholar]
  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
    [Google Scholar]
  31. McGeoch D. J., Moss H. W. M., McNab D., Frame M. C. 1987; DNA sequence and genetic content of the Hin dIII 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
    [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
    [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 Van Regenmortel M. H. V., Neurath A. R.
    [Google Scholar]
  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
    [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
    [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
    [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
    [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
    [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
    [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
    [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
    [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
    [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
    [Google Scholar]
/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...

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