Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1984 Jun;50(3):805–812. doi: 10.1128/jvi.50.3.805-812.1984

Immunogenicity of herpes simplex virus glycoproteins gC and gB and their role in protective immunity.

J Glorioso, C H Schröder, G Kumel, M Szczesiul, M Levine
PMCID: PMC255740  PMID: 6328010

Abstract

The relative antigenicity of the individual herpes simplex virus type 1 (KOS) glycoproteins gC and gB was analyzed in BALB/c mice by using KOS mutants altered in their ability to present these antigens on cell surface membranes during infection. The mutants employed were as follows: syn LD70 , a non-temperature-sensitive mutant defective in the synthesis of cell surface membrane gC; tsF13 , a temperature-sensitive mutant defective in the processing of the precursor form of gB to the mature cell surface form at 39 degrees C; and ts606 , an immediate early temperature-sensitive mutant defective in the production of all early and late proteins including the glycoproteins. By comparing the relative susceptibility to immunolysis of mouse 3T3 cells infected at 39 degrees C with wild-type virus, presenting the full complement of the glycoprotein antigens, gC, gB, and gD, with target cells infected with mutants presenting only subsets of these antigens, we determined that a major portion of cytolytic antibody contained in hyperimmune anti-herpes simplex virus type 1 (KOS) mouse antiserum was directed against glycoproteins gC and gB. The relative immunogenicity of wild-type and mutant virus-infected cells also was compared in BALB/c mice. Immunogen lacking the mature form of gB induced a cytolytic antibody titer comparable to that of the wild-type virus, whereas that lacking the mature form of gC showed a 70% reduction in titer. The absence of the mature cell surface forms of gB and gC in immunogen preparations resulted in a 4- to 15-fold reduction in in virus neutralizing titer. Animals immunized with ts606 -infected cells (39 degrees C) induced relatively little virus-specific cytolytic and neutralizing antibody. Analysis of the glycoprotein specificities of these antisera by radioimmunoprecipitation showed that the antigens immunoprecipitated reflected the viral plasma membrane glycoprotein profiles of the immunogens. The absence of the mature forms of gC or gB in the immunizing preparation did not appreciably affect the immunoprecipitating antibody response to other antigens. Mice immunized with wild-type and mutant virus-infected cells were tested for their resistance to intracranial and intraperitoneal challenge with the highly virulent WAL strain of herpes simplex virus type 1. Despite the observed alterations in serum virus-specific antibody induced with the individual immunogens, all animals survived an intraperitoneal challenge of 10 50% lethal doses. However, differences in the survival of animals were obtained upon intracranial challenge.(ABSTRACT TRUNCATED AT 400 WORDS)

Full text

PDF
805

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Balachandran N., Bacchetti S., Rawls W. E. Protection against lethal challenge of BALB/c mice by passive transfer of monoclonal antibodies to five glycoproteins of herpes simplex virus type 2. Infect Immun. 1982 Sep;37(3):1132–1137. doi: 10.1128/iai.37.3.1132-1137.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baron S., Worthington M. G., Williams J., Gaines J. W. Postexposure serum prophylaxis of neonatal herpes simplex virus infection of mice. Nature. 1976 Jun 10;261(5560):505–506. doi: 10.1038/261505a0. [DOI] [PubMed] [Google Scholar]
  3. Bishop G. A., Glorioso J. C., Schwartz S. A. Role of interferon in human natural killer activity against target cells infected with HSV-1. J Immunol. 1983 Oct;131(4):1849–1853. [PubMed] [Google Scholar]
  4. Carter V. C., Schaffer P. A., Tevethia S. S. The involvement of herpes simplex virus type 1 glycoproteins in cell-mediated immunity. J Immunol. 1981 May;126(5):1655–1660. [PubMed] [Google Scholar]
  5. Chan W. L. Protective immunization of mice with specific HSV-1 glycoproteins. Immunology. 1983 Jun;49(2):343–352. [PMC free article] [PubMed] [Google Scholar]
  6. Davis W. B., Taylor J. A., Oakes J. E. Ocular infection with herpes simplex virus type 1: prevention of acute herpetic encephalitis by systemic administration of virus-specific antibody. J Infect Dis. 1979 Oct;140(4):534–540. doi: 10.1093/infdis/140.4.534. [DOI] [PubMed] [Google Scholar]
  7. Dix R. D., Pereira L., Baringer J. R. Use of monoclonal antibody directed against herpes simplex virus glycoproteins to protect mice against acute virus-induced neurological disease. Infect Immun. 1981 Oct;34(1):192–199. doi: 10.1128/iai.34.1.192-199.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Eberle R., Courtney R. J. Assay of type-specific and type-common antibodies to herpes simplex virus types 1 and 2 in human sera. Infect Immun. 1981 Mar;31(3):1062–1070. doi: 10.1128/iai.31.3.1062-1070.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Eberle R., Courtney R. J. Preparation and characterization of specific antisera to individual glycoprotein antigens comprising the major glycoprotein region of herpes simplex virus type 1. J Virol. 1980 Sep;35(3):902–917. doi: 10.1128/jvi.35.3.902-917.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gilman S. C., Docherty J. J., Rawls W. E. Antibody responses in humans to individual proteins of herpes simplex viruses. Infect Immun. 1981 Dec;34(3):880–887. doi: 10.1128/iai.34.3.880-887.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Glorioso J. C., Smith J. W. Immune interactions with cells infected with herpes simplex virus: antibodies to radioiodinated surface antigens. J Immunol. 1977 Jan;118(1):114–121. [PubMed] [Google Scholar]
  12. Glorioso J., Szczesiul M. S., Marlin S. D., Levine M. Inhibition of glycosylation of herpes simplex virus glycoproteins: identification of antigenic and immunogenic partially glycosylated glycopeptides on the cell surface membrane. Virology. 1983 Apr 15;126(1):1–18. doi: 10.1016/0042-6822(83)90458-0. [DOI] [PubMed] [Google Scholar]
  13. Kapoor A. K., Buckmaster A., Nash A. A., Field H. J., Wildy P. Role of neutralizing antibodies and T-cells in pathogenesis of herpes simplex virus infection in congenitally athymic mice. Immunol Lett. 1982 Nov;5(5):259–265. doi: 10.1016/0165-2478(82)90109-2. [DOI] [PubMed] [Google Scholar]
  14. Kapoor A. K., Nash A. A., Wildy P., Phelan J., McLean C. S., Field H. J. Pathogenesis of herpes simplex virus in congenitally athymic mice: the relative roles of cell-mediated and humoral immunity. J Gen Virol. 1982 Jun;60(Pt 2):225–233. doi: 10.1099/0022-1317-60-2-225. [DOI] [PubMed] [Google Scholar]
  15. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  16. Luyet F., Samra D., Soneji A., Marks M. I. Passive immunization in experimental Herpesvirus hominis infection of newborn mice. Infect Immun. 1975 Dec;12(6):1258–1261. doi: 10.1128/iai.12.6.1258-1261.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. McKendall R. R. Efficacy of herpes simplex virus type 1 immunization in protecting against acute and latent infection by herpes simplex virus type 2 in mice. Infect Immun. 1977 May;16(2):717–719. doi: 10.1128/iai.16.2.717-719.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Morahan P. S., Thomson T. A., Kohl S., Murray B. K. Immune responses to labial infection of BALB/c mice with herpes simplex virus type 1. Infect Immun. 1981 Apr;32(1):180–187. doi: 10.1128/iai.32.1.180-187.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Norrild B., Shore S. L., Nahmias A. J. Herpes simplex virus glycoproteins: participation of individual herpes simplex virus type 1 glycoprotein antigens in immunocytolysis and their correlation with previously identified glycopolypeptides. J Virol. 1979 Dec;32(3):741–748. doi: 10.1128/jvi.32.3.741-748.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Oakes J. E., Davis W. B., Taylor J. A., Weppner W. A. Lymphocyte reactivity contributes to protection conferred by specific antibody passively transferred to herpes simplex virus-infected mice. Infect Immun. 1980 Aug;29(2):642–649. doi: 10.1128/iai.29.2.642-649.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Oakes J. E., Lausch R. N. Role of Fc fragments in antibody-mediated recovery from ocular and subcutaneous herpes simplex virus infections. Infect Immun. 1981 Jul;33(1):109–114. doi: 10.1128/iai.33.1.109-114.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Oakes J. E., Rosemond-Hornbeak H. Antibody-mediated recovery from subcutaneous herpes simplex virus type 2 infection. Infect Immun. 1978 Aug;21(2):489–495. doi: 10.1128/iai.21.2.489-495.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Pereira L., Klassen T., Baringer J. R. Type-common and type-specific monoclonal antibody to herpes simplex virus type 1. Infect Immun. 1980 Aug;29(2):724–732. doi: 10.1128/iai.29.2.724-732.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rector J. T., Lausch R. N., Oakes J. E. Use of monoclonal antibodies for analysis of antibody-dependent immunity to ocular herpes simplex virus type 1 infection. Infect Immun. 1982 Oct;38(1):168–174. doi: 10.1128/iai.38.1.168-174.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schrier R. D., Pizer L. I., Moorhead J. W. Type-specific delayed hypersensitivity and protective immunity induced by isolated herpes simplex virus glycoprotein. J Immunol. 1983 Mar;130(3):1413–1418. [PubMed] [Google Scholar]
  26. Schröder C. H., Kümel G., Glorioso J., Kirchner H., Kaerner H. C. Neuropathogenicity of herpes simplex virus in mice: protection against lethal encephalitis by co-infection with a non-encephalitogenic strain. J Gen Virol. 1983 Sep;64(Pt 9):1973–1982. doi: 10.1099/0022-1317-64-9-1973. [DOI] [PubMed] [Google Scholar]
  27. Schröeder C. H., Engler H., Kirchner H. Protection of mice by an apathogenic strain HSV-1 against lethal infection by a pathogenic strain of HSV-1. J Gen Virol. 1981 Jan;52(Pt 1):159–161. doi: 10.1099/0022-1317-52-1-159. [DOI] [PubMed] [Google Scholar]
  28. Shore S. L., Cromeans T. L., Norrild B. Early damage of herpes-infected cells by antibody-dependent cellular cytotoxicity: relative roles of virus-specified cell-surface antigens and input virus. J Immunol. 1979 Nov;123(5):2239–2244. [PubMed] [Google Scholar]
  29. Vestergaard B. F. Herpes simplex virus antigens and antibodies: a survey of studies based on quantitative immunoelectrophoresis. Rev Infect Dis. 1980 Nov-Dec;2(6):899–913. doi: 10.1093/clinids/2.6.899. [DOI] [PubMed] [Google Scholar]
  30. Weber K., Osborn M. The reliability of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis. J Biol Chem. 1969 Aug 25;244(16):4406–4412. [PubMed] [Google Scholar]
  31. Zweerink H. J., Martinez D., Lynch R. J., Stanton L. W. Immune responses in mice against herpes simplex virus: mechanisms of protection against facial and ganglionic infections. Infect Immun. 1981 Jan;31(1):267–275. doi: 10.1128/iai.31.1.267-275.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Zweerink H. J., Stanton L. W. Immune response to herpes simplex virus infections: virus-specific antibodies in sera from patients with recurrent facial infections. Infect Immun. 1981 Feb;31(2):624–630. doi: 10.1128/iai.31.2.624-630.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES