1887

Abstract

Glycoprotein gp116 of human cytomegalovirus (HCMV) is a target for neutralizing antibodies. Gp116 is a component of the gCI complex which consists of gp58 and gp116. Like its homologue, glycoprotein B of herpes simplex virus type 1, gp116 contains a highly antigenic region in the N-terminal part of the molecule, between amino acids 28 and 84. Prokaryotic expression plasmids and synthetic peptides were used to define binding sites for mouse and human monoclonal antibodies (MAbs) as well as HCMV convalescent sera. Site I, located between amino acids 68 and 77, contains an epitope recognized by the human MAb C23, which is capable of neutralizing HCMV independently of complement and the site is conserved between HCMV strains. Of HCMV-positive human sera, 53% recognized site I. Site II was mapped using mouse MAbs as well as human sera. It is located between residues 50 and 54, an area which is not conserved between strains AD169 and Towne, the two laboratory strains of known sequence. Strain-specific antibodies were detected in 25% of human sera. Site II-specific antibodies, purified from human sera by affinity chromatography, were found to be incapable of neutralizing HCMV in tissue culture.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-73-9-2375
1992-09-01
2024-04-20
Loading full text...

Full text loading...

/deliver/fulltext/jgv/73/9/JV0730092375.html?itemId=/content/journal/jgv/10.1099/0022-1317-73-9-2375&mimeType=html&fmt=ahah

References

  1. Alp N. J., Allport T. D., Van-Zanten J., Rodgers B., Sissons J. G., Borysiewicz L. K. 1991; Fine specificity of cellular immune responses in humans to human cytomegalovirus immediateearly 1 protein. Journal of Virology 65:4812–4820
    [Google Scholar]
  2. Andreoni M., Faircloth M., Vugler L., Britt W. J. 1989; A rapid microneutralization assay for the measurement of neutralizing antibody reactive with human cytomegalovirus. Journal of Virological Methods 23:157–167
    [Google Scholar]
  3. Baboonian C., Blake K., Booth J. C., Wiblin C. N. 1989; Complement-independent neutralising monoclonal antibody with differential reactivity for strains of human cytomegalovirus. Journal of Medical Virology 29:139–145
    [Google Scholar]
  4. Banks T., Huo B., Kousoulas K., Spaete R., Pachl C., Pereira L. 1989; A major neutralizing domain maps within the carboxyl-terminal half of the cleaved cytomegalovirus B glycoprotein. Journal of General Virology 70:979–985
    [Google Scholar]
  5. Basgoz N., Qadri I., Navarro D., Sears A., Lennette E., Youngblom J., Pereira L. 1992; The amino terminus of human cytomegalovirus glycoprotein B contains epitopes that vary among strains. Journal of General Virology 73:983–988
    [Google Scholar]
  6. Borysiewicz L. K., Hickling J. K., Graham S., Sinclair J., Cranage M. P., Smith G. L., Sissons J. G. 1988; Human cytomegalovirus-specific cytotoxic T cells. Relative frequency of stage-specific CTL recognizing the 72-kD immediate early protein and glycoprotein B expressed by recombinant vaccinia viruses. Journal of Experimental Medicine 168:919–931
    [Google Scholar]
  7. Britt W. J. 1984; Neutralizing antibodies detect a disulfide-linked glycoprotein complex within the envelope of human cytomegalovirus. Virology 135:369–378
    [Google Scholar]
  8. Britt W. J., Vugler L. G. 1989; Processing of the gp55-l 16 envelope glycoprotein complex (gB) of human cytomegalovirus. Journal of Virology 63:403–410
    [Google Scholar]
  9. Britt W. J., Vugler L., Butfiloski E. J., Stephens E. B. 1990; Cell surface expression of human cytomegalovirus (HCMV) gp55-116 (gB): use of HCMV-recombinant vaccinia virus-infected cells in analysis of the human neutralizing antibody response. Journal of Virology 64:1079–1085
    [Google Scholar]
  10. Chou S. W., Dennison K. M. 1991; Analysis of interstrain variation in cytomegalovirus glycoprotein B sequences encoding neutralization-related epitopes. Journal of Infectious Diseases 163:1229–1234
    [Google Scholar]
  11. Cranage M. P., Kouzarides T., Bankier A. T., Satchwell S., Weston K., Tomlinson P., Barrell B., Hart H., Bell S. E., Minson A. C. 1986; Identification of the human cytomegalovirus glycoprotein B gene and induction of neutralizing antibodies via its expression in recombinant vaccinia virus. EMBO Journal 5:3057–3063
    [Google Scholar]
  12. Ehrlich P. H., Harfeldt K. E., Justice J. C., Moustafa Z. A., Ostberg L. 1987; Rhesus monkey responses to multiple injections of human monoclonal antibodies. Hybridoma 6:151–160
    [Google Scholar]
  13. Farrell H. E., Shellam G. R. 1991; Protection against murine cytomegalovirus infection by passive transfer of neutralizing and non-neutralizing monoclonal antibodies. Journal of General Virology 72:149–156
    [Google Scholar]
  14. Gonczol E., Plotkin S. 1990; Progress in vaccine development for prevention of human cytomegalovirus infection. Current Topics in Microbiology and Immunology 154:255–274
    [Google Scholar]
  15. Gretch D. R., Gehrz R. C., Stinski M. F. 1988; Characterization of a human cytomegalovirus glycoprotein complex (gcI). Journal of General Virology 69:1205–1215
    [Google Scholar]
  16. Hayes K., Alford C., Britt W. 1987; Antibody response to virus-encoded proteins after cytomegalovirus mononucleosis. Journal of Infectious Diseases 156:615–621
    [Google Scholar]
  17. Highlander S. L., Cai W. H., Person S., Levine M., Glorioso J. C. 1988; Monoclonal antibodies define a domain on herpes simplex virus glycoprotein B involved in virus penetration. Journal of Virology 62:1881–1888
    [Google Scholar]
  18. Highlander S. L., Dorney D. J., Gage P. J., Holland T. C., Cai W., Person S., Levine M., Glorioso J. C. 1989; Identification of mar mutations in herpes simplex virus type 1 glycoprotein B which alter antigenic structure and function in virus penetration. Journal of Virology 63:730–738
    [Google Scholar]
  19. Houghten R. A. 1985; General method for rapid solid-phase synthesis of large numbers of peptides: specificity of antigen-antibody interaction at level of individual amino acids. Proceedings of the National Academy of Sciences, U.S.A. 82:5131–5135
    [Google Scholar]
  20. Kari B., Liu Y.-N. C., Goertz R., Lussenhop N., Stinski M. F., Gehrz R. 1990; Structure and composition of a family of human cytomegalovirus glycoprotein complexes designated gC-I (gB). Journal of General Virology 71:2673–2680
    [Google Scholar]
  21. Knapp S., Broker M., Amann E. 1990; pSEM vectors: high level expression of antigenic determinants and protein domains. Biotechniques 8:280–281
    [Google Scholar]
  22. Kniess N., Mach M., Fay J., Britt W. J. 1991; Distribution of linear antigenic sites on glycoprotein gp55 of human cytomegalovirus. Journal of Virology 65:138–146
    [Google Scholar]
  23. Kousoulas K., Arsenakis M., Pereira L. 1989; A subset of type-specific epitopes map in the amino terminus of herpes simplex virus type 1 glycoprotein B. Journal of General Virology 70:735–741
    [Google Scholar]
  24. Landini M. P., Re M. C., Mirolo G., Baldassarri B., LaPlaca M. 1985; Human immune response to cytomegalovirus structural polypeptides studied by immunoblotting. Journal of Medical Virology 17:303–311
    [Google Scholar]
  25. Lehner R., Stamminger T., Mach M. 1991; Comparative sequence analysis of human cytomegalovirus strains. Journal of Clinical Microbiology 29:2494–2502
    [Google Scholar]
  26. Liu Y. N., Kari B., Gehrz R. C. 1988; Human immune responses to major human cytomegalovirus glycoprotein complexes. Journal of Virology 62:1066–1070
    [Google Scholar]
  27. Liu Y.-N., Opitz G., Klaus A., Cooper J., Gehrz R. C. 1991; Helper T cell epitope mapping of gB glycoproteins of human cytomegalovirus (HCMV). In Progress in Cytomegalovirus Research pp 187–190 Edited by Landini M. P. Amsterdam: Elsevier;
    [Google Scholar]
  28. Lussenhop N. O., Goertz R., Wabuke-Bunoti M., Gehrz R., Kari B. 1988; Epitope analysis of human cytomegalovirus glycoprotein complexes using murine monoclonal antibodies. Virology 164:362–372
    [Google Scholar]
  29. Mach M., Utz U., Fleckenstein B. 1986; Mapping of the major glycoprotein gene of human cytomegalovirus. Journal of General Virology 67:1461–1467
    [Google Scholar]
  30. Masuho Y., Matsumoto Y.-L., Sugano T., Fujinaga S., Minamishima Y. 1987; Human monoclonal antibodies neutralizing human cytomegalovirus. Journal of General Virology 68:1457–1461
    [Google Scholar]
  31. Meyer H., Masuho Y., Mach M. 1990; The gp116 of the gp58/116 complex of human cytomegalovirus represents the amino-terminal part of the precursor molecule and contains a neutralizing epitope. Journal of General Virology 71:2443–2450
    [Google Scholar]
  32. Nowak B., Sullivan C., Sarnow P., Thomas R., Bricout F., Nicolas J. C., Fleckenstein B., Levine A. J. 1984; Characterization of monoclonal antibodies and polyclonal immune sera directed against human cytomegalovirus virion proteins. Virology 132:325–338
    [Google Scholar]
  33. Pereira L., Hoffman M. 1986; Immunology of human cytomegalovirus glycoproteins. In Human Herpesvirus Infections : Pathogenesis, Diagnosis and Treatment pp 69–92 Edited by Lopez C., Roizman B. New York: Raven Press;
    [Google Scholar]
  34. Pereira L., Hoffman M., Gallo D., Cremer N. 1982; Monoclonal antibodies to human cytomegalovirus: three surface membrane proteins with unique immunological and electrophoretic properties specify cross-reactive determinants. Infection and Immunity 36:924–932
    [Google Scholar]
  35. Pereira L., Ali M., Kousoulas K., Huo B., Banks T. 1989; Domain structure of herpes simplex virus 1 glycoprotein B: neutralizing epitopes map in regions of continuous and discontinuous residues. Virology 172:11–24
    [Google Scholar]
  36. Rasmussen L. E., Nelson R. M., Kelsall D. C., Merigan T. C. 1984; Murine monoclonal antibody to a single protein neutralizes the infectivity of human cytomegalovirus. Proceedings of the National Academy of Sciences, U.S.A. 81:876–880
    [Google Scholar]
  37. Rasmussen L., Mullenax J., Nelson M., Merigan T. C. 1985a; Human cytomegalovirus polypeptides stimulate neutralizing antibody in vivo . Virology 145:186–190
    [Google Scholar]
  38. Rasmussen L., Mullenax J., Nelson R., Merigan T. C. 1985b; Viral polypeptides detected by a complement-dependent neutralizing murine monoclonal antibody to human cytomegalovirus. Journal of Virology 55:274–280
    [Google Scholar]
  39. SÄllberg M., Ruden U., Magnius L. O., Norrby E., Wahren B. 1991; Rapid “Tbag” peptide synthesis using 9-fluoroenylmeth-oxycarbonyl (Fmoc) protected amino acids for immunological mapping of viral proteins. Immunological Letters 30:59–68
    [Google Scholar]
  40. Sambrook J., Fritsch E. F., Maniatis T. 1989 Molecular Cloning: A Laboratory Manual 2nd edn New York: Cold Spring Harbor Laboratory;
    [Google Scholar]
  41. Sanger F., Nicklen S., Coulson A. R. 1977; DNA sequencing with chain-terminating inhibitors. Proceedings of the National Academy of Sciences, U.S.A. 74:5463–5467
    [Google Scholar]
  42. Silvestri M., Sundqvist V.-A., Ruden U., Wahren B. 1991; Characterization of a major antigenic region on gp55 of human cytomegalovirus. Journal of General Virology 72:3017–3023
    [Google Scholar]
  43. Spaete R. R., Thayer R. M., Probert W. S., Masiarz F. R., Chamberlain S. H., Rasmussen L., Merigan T. C., Pachl C. 1988; Human cytomegalovirus strain Towne glycoprotein B is processed by proteolytic cleavage. Virology 167:207–225
    [Google Scholar]
  44. Spaete R. R., Saxena A., Scott P. I., Song G. J., Probert W. S., Britt W. J., Gibson W., Rasmussen L., Pachl C. 1990; Sequence requirements for proteolytic processing of glycoprotein B of human cytomegalovirus strain Towne. Journal of Virology 64:2922–2931
    [Google Scholar]
  45. Tomiyama T., Masuho M. 1990; Antiviral activities of a human monoclonal antibody against human cytomegalovirus. In Immunobiology and Prophylaxis of Human Herpesvirus Infections pp 105–113 Edited by Lopez C. New York: Plenum Press;
    [Google Scholar]
  46. Urban M., Britt W., Mach M. 1992; The dominant linear neutralizing antibody-binding site of glycoprotein gp86 of human cytomegalovirus is strain specific. Journal of Virology (in press)
    [Google Scholar]
  47. Utz U., Britt W., Vugler L., Mach M. 1989; Identification of a neutralizing epitope on glycoprotein gp58 of human cytomegalovirus. Journal of Virology 63:1995–2001
    [Google Scholar]
  48. Waner J. L., Weller T. H. 1978; Analysis of antigenic diversity among human cytomegaloviruses by kinetic neutralization tests with high-titered rabbit antisera. Infection and Immunity 21:151–157
    [Google Scholar]
  49. Xu-bin Murayama T., Ishida K., Furukawa T. 1989; Characterization of IgG Fc receptors induced by human cytomegalovirus. Journal of General Virology 70:893–900
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-73-9-2375
Loading
/content/journal/jgv/10.1099/0022-1317-73-9-2375
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