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Analysis of human antibody responses to human cytomegalovirus envelope glycoproteins found in two families of disulfide linked glycoprotein complexes designated gC-I and gC-II

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Summary

Human antibody responses to human cytomegalovirus (HCMV) envelope glycoproteins were analyzed using immunoaffinity purified glycoproteins and Western blotting. Two families of disulfide linked glycoprotein complexes, designated gC-I and gC-II, were isolated. These complexes were reduced and their individual glycoproteins separated by polyacrylamide gel electrophoresis prior to electroblotting. The reactivity of adult convalescent sera with individual glycoproteins was compared to that of sera from congenitally infected infants. All sera tested reacted with a 52,000 molecular weight glycoprotein from these complexes, but only 75% reacted with a 93,000 to 130,000 molecular weight glycoprotein from gC-I complexes. Most adult convalescent sera reacted with glycoproteins from gC-II complexes. However, 14 of 16 infant sera did not have high enough levels of gC-II antibodies to give a positive reaction with Western blotting. A longitudinal study was done with several infants and their mothers. These studies indicated a failure by the infants and their mothers to develop detectable levels of gC-II antibodies months to years after the initial infection or after repeated stimulation with HCMV due to persistent infection. The inability of these infants to develop significant levels of gC-II antibodies was not due to an inability to respond to viral glycoproteins since they had antibodies to gC-I glycoproteins. We also determined that the strains of HCMV infecting some of these infants expressed gC-II glycoproteins. Thus, the lack of response by these infants was not due to lack of expression of gC-II glycoproteins by their infecting strain.

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References

  1. Alford CA, Hayes K, Britt W (1988) Primary cytomegalovirus infection in pregnancy: comparison of antibody responses to virus-encoded proteins between women with and without intrauterine infection. J Infect Dis 158: 917–924

    Google Scholar 

  2. Banks T, Huo B, Kousoulas K, Spaete R, Pachl C, Pereira L (1989) A major neutralizing domain maps with the carboxyl-terminal half of the cleaved cytomegalovirus B glycoprotein. J Gen Virol 70: 979–985

    Google Scholar 

  3. Britt WJ (1984) Neutralizing antibodies detect a disulfide-linked glycoprotein complex within the envelope of human cytomegalovirus. Virology 135: 369–378

    Google Scholar 

  4. Britt WJ, Auger D (1986) Synthesis and processing of the envelope gp 55–116 complex of human cytomegalovirus. J Virol 58: 185–191

    Google Scholar 

  5. Britt WJ, Vugler L, Stephens EB (1988) Induction of complement-dependent and - independent neutralizing antibodies by recombinant-derived human cytomegalovirus gp 55–116 (gB). J Virol 62: 3309–3318

    Google Scholar 

  6. Britt WJ, Vugler LG (1989) Processing of gp 55–116 envelope glycoprotein complex (gB) of human cytomegalovirus. J Virol 63: 403–410

    Google Scholar 

  7. Cranage MP, Kouzarides T, Bankier AT, Satchwell S, Weston K, Tomlinson P, Barrell B, Hart H, Bell SE, Minson AC, Smith GL (1986) Identification of the human cytomegalovirus glycoprotein B gene and induction of neutralizing antibodies via its expression in recombinant vaccinia virus. EMBO J 5: 3057–3063

    Google Scholar 

  8. Farrar GH, Greenaway PJ (1986) Characterization of glycoprotein complexes present in human cytomegalovirus envelopes. J Gen Virol 65: 1991–2001

    Google Scholar 

  9. Gallagher P, Henneberry J, Wilson I, Sambrook J, Gething M-J (1988) Addition of carbohydrate side chains at novel sites on influenza virus hemagglutinin can modulate folding, transport, and activity of the molecule. J Cell Biol 107: 2059–2073

    Google Scholar 

  10. Gehrz RC, Marker SC, Knorr SO, Kalis JM, Balfour HH Jr (1977) Specific cell-mediated immune defect in active cytomegalovirus infection of young children and their mothers. Lancet 2: 844–847

    Google Scholar 

  11. Gehrz RC, Linner KM, Christianson WR, Ohm A, Balfour HH Jr (1982) Cytomegalovirus infection in infancy: virological and immunological studies. Clin Exp Immunol 47: 27–33

    Google Scholar 

  12. Gehrz RC, Peterson ES, Liu Y-NC (1988) Immune mechanisms in congential cytomegalovirus infection: activation of CMV-specific T helper cells (CMV-Th) by exogenous IL-2. Clin Exp Immunol 74: 333–338

    Google Scholar 

  13. Gold D, Ashley R, Handsfield HH, Verdon M, Leach L, Mills J, Drew L, Corey L (1988) Immunoblot analysis of the humoral immune response in primary cytomegalovirus infection. J Infect Dis 157: 319–326

    Google Scholar 

  14. Gonczol E, Ianacone J, Furlini G, Ho W, Plotkin SA (1989) Humoral immune response to cytomegalovirus Towne vaccine strain and to Toledo low-passage strain. J Infect Dis 139: 851–859

    Google Scholar 

  15. Gretch DR, Suter M, Stinski MF (1987) The use of biotinylated monoclonal antibodies and streptavidin affinity chromatography to isolate herpesvirus hydrophobic proteins or glycoproteins. Anal Biochem 163: 270–277

    Google Scholar 

  16. Gretch DR, Kari B, Rasmussen L, Gehrz RC, Stinski MF (1988) Identification and characterization of three distinct families of glycoprotein complexes in the envelope of human cytomegalovirus. J Virol 62: 875–881

    Google Scholar 

  17. Gretch DR, Gehrz RC, Stinski MF (1988) Characterization of a human cytomegalovirus glycoprotein complex (gc I). J Gen Virol 69: 1205–1215

    Google Scholar 

  18. Gretch DR, Kari B, Gehrz RC, Stinski MF (1988) A multigene family encodes the human cytomegalovirus glycoprotein complex gc II (gp 47–52 complex). J Virol 62: 1956–1962

    Google Scholar 

  19. Hayes K, Alford C, Britt W (1987) Antibody response to virus-encoded proteins after cytomegalovirus mononucleosis. J Infect Dis 156: 615–621

    Google Scholar 

  20. Ho M (1982) Cytomegalovirus biology and infection. In: Grennough III WB, Merigan TC (eds) Current topics in infectious disease. Plenum, New York

    Google Scholar 

  21. Kari B, Lussenhop N, Goertz R, Wabuke-Bunoti M, Radeke R, Gehrz R (1986) Characterization of monoclonal antibodies reactive to several biochemically distinct human cytomegalovirus glycoprotein complexes. J Virol 60: 345–352

    Google Scholar 

  22. Kari B, Gehrz R (1988) Isolation and characterization of a human cytomegalovirus glycoprotein containing a high content of O-linked oligosaccharides. Arch Virol 98: 171–188

    Google Scholar 

  23. Kari B, Goertz R, Gehrz R (1990) Characterization of cytomegalovirus glycoproteins in a family of complexes designated gC-II with murine monoclonal antibodies. Arch Virol 112: 55–65

    Google Scholar 

  24. Landini MP, Re MC, Mirolo G, Baldassarri B, LaPlaca M (1985) Human immune response to cytomegalovirus structural polypeptides studied by immunoblotting. J Med Virol 17: 303–311

    Google Scholar 

  25. Laemmli UK (1970) Cleavage of structural proteins during assembly of the head of bacteriophage T 4. Nature 277: 680–684

    Google Scholar 

  26. Liu Y-NC, Kari B, Gehrz RC (1988) Human immune responses to major human cytomegalovirus glycoprotein complexes. J Virol 62: 1066–1070

    Google Scholar 

  27. Lussenhop N, 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 

  28. Mirolo G, Baldassarri B, Ripati A, Re MC, Clementi M, Manzin A, Landini MP (1986) Antibody response to individual cytomegalovirus structural proteins in different groups of subjects. Eur J Clin Microbiol 6: 207–210

    Google Scholar 

  29. Pereira L, Hoffman M, Cremer N (1982) Electrophoretic analysis of polypeptides immune precipitated from cytomegalovirus-infected cell extracts by human sera. Infect Immun 36: 933–942

    Google Scholar 

  30. Pereira L, Stagno S, Hoffman M, Volanakis JE (1983) Cytomegalovirus-infected cell polypeptides immune-precipitated by sera from children with congenital and perinatal infections. Infect Immun 39: 100–108

    Google Scholar 

  31. Porath A, Hanuka N, Keynan A, Sarov I (1987) Virus specific serum IgG, IgM, and IgA antibodies in cytomegalovirus mononucleosis patients as determined by immunoblotting technique. J Med Virol 22: 223–230

    Google Scholar 

  32. Rasmussen L, Mullenax J, Nelson R, Merigan TC (1985) Viral polypeptides detected by a complement dependent neutralizing murine monoclonal antibody to human cytomegalovirus. J Virol 55: 274–280

    Google Scholar 

  33. Spaete RR, Thayer RM, Probert WS, Masiarz FR, Chamberlin SH, Rasmussen L, Merigan TC, Pachl C (1988) Human cytomegalovirus strain Towne glycoprotein B is processed by proteolytic cleavage. Virology 167: 207–225

    Google Scholar 

  34. Taylor DL, Fellows LE, Farrar GH, Nash RJ, Taylor-Robinson D, Mobberley MA, Ryder TA, Jeffries DJ, Tyms AS (1988) Loss of infectivity after treatment with castanospermine or related plant alkaloids correlates with aberrant glycoprotein synthesis. Antiviral Res 10: 11–26

    Google Scholar 

  35. Weston K, Barrell BG (1986) Sequence of the short unique region, short repeats, and part of the long repeats of human cytomegalovirus. J Mol Biol 192: 177–208

    Google Scholar 

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Kari, B., Gehrz, R. Analysis of human antibody responses to human cytomegalovirus envelope glycoproteins found in two families of disulfide linked glycoprotein complexes designated gC-I and gC-II. Archives of Virology 114, 213–228 (1990). https://doi.org/10.1007/BF01310750

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  • DOI: https://doi.org/10.1007/BF01310750

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