Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1986 Nov;60(2):470–475. doi: 10.1128/jvi.60.2.470-475.1986

Binding of complement component C3b to glycoprotein gC of herpes simplex virus type 1: mapping of gC-binding sites and demonstration of conserved C3b binding in low-passage clinical isolates.

H M Friedman, J C Glorioso, G H Cohen, J C Hastings, S L Harris, R J Eisenberg
PMCID: PMC288914  PMID: 3021981

Abstract

The sites on glycoprotein gC of herpes simplex virus type 1 (HSV-1) which bind complement component C3b were evaluated by using anti-gC monoclonal antibodies and mutants which have alterations at defined regions of the glycoprotein. Monoclonal antibodies were incubated with HSV-1-infected cells in a competitive assay to block C3b binding. Each of 12 different monoclonals, which recognize the four major antigenic sites of gC, completely inhibited C3b binding. With this approach, no one antigenic group on gC could be assigned as the C3b-binding region. Next, 21 gC mutants were evaluated for C3b binding, including 1 which failed to synthesize gC, 4 which synthesized truncated forms of the glycoprotein such that gC did not insert into the cell's membrane, and 16 which expressed gC on the cell's surface but which had mutations in various antigenic groups. Eleven strains did not bind C3b. This included the 1 strain which did not synthesize gC, the 4 strains which secreted gC without inserting the glycoprotein into the cell membrane, and 6 of 16 strains which expressed gC on the cell surface. In these six strains, the mutations were at three different antigenic sites. One hypothesis to explain these findings is that C3b binding is modified by changes in the conformation of gC which develop either after antibodies bind to gC or as a result of mutations in the gC gene. Attachment of C3b to gC was also evaluated in 31 low-passage clinical isolates of HSV-1. Binding was detected with each HSV-1 isolate, but not with nine HSV-2 isolates. Therefore, although mutants that lack C3b binding are readily selected in vitro, the C3b-binding function of gC is maintained in vivo. These results indicate that the sites on gC that bind C3b are different from those that bind monoclonal antibodies, that antibodies directed against all sites on gC block C3b binding, and that C3b binding is a conserved function of gC in vivo.

Full text

PDF
470

Selected References

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

  1. Adler R., Glorioso J. C., Cossman J., Levine M. Possible role of Fc receptors on cells infected and transformed by herpesvirus: escape from immune cytolysis. Infect Immun. 1978 Aug;21(2):442–447. doi: 10.1128/iai.21.2.442-447.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baucke R. B., Spear P. G. Membrane proteins specified by herpes simplex viruses. V. Identification of an Fc-binding glycoprotein. J Virol. 1979 Dec;32(3):779–789. doi: 10.1128/jvi.32.3.779-789.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bishop G. A., Kümel G., Schwartz S. A., Glorioso J. C. Specificity of human natural killer cells in limiting dilution culture for determinants of herpes simplex virus type 1 glycoproteins. J Virol. 1986 Jan;57(1):294–300. doi: 10.1128/jvi.57.1.294-300.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Buckmaster E. A., Gompels U., Minson A. Characterisation and physical mapping of an HSV-1 glycoprotein of approximately 115 X 10(3) molecular weight. Virology. 1984 Dec;139(2):408–413. doi: 10.1016/0042-6822(84)90387-8. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Centifanto-Fitzgerald Y. M., Yamaguchi T., Kaufman H. E., Tognon M., Roizman B. Ocular disease pattern induced by herpes simplex virus is genetically determined by a specific region of viral DNA. J Exp Med. 1982 Feb 1;155(2):475–489. doi: 10.1084/jem.155.2.475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chou P. Y., Fasman G. D. Conformational parameters for amino acids in helical, beta-sheet, and random coil regions calculated from proteins. Biochemistry. 1974 Jan 15;13(2):211–222. doi: 10.1021/bi00699a001. [DOI] [PubMed] [Google Scholar]
  8. Chou P. Y., Fasman G. D. Prediction of protein conformation. Biochemistry. 1974 Jan 15;13(2):222–245. doi: 10.1021/bi00699a002. [DOI] [PubMed] [Google Scholar]
  9. Cines D. B., Lyss A. P., Bina M., Corkey R., Kefalides N. A., Friedman H. M. Fc and C3 receptors induced by herpes simplex virus on cultured human endothelial cells. J Clin Invest. 1982 Jan;69(1):123–128. doi: 10.1172/JCI110422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cohen G. H., Dietzschold B., Ponce de Leon M., Long D., Golub E., Varrichio A., Pereira L., Eisenberg R. J. Localization and synthesis of an antigenic determinant of herpes simplex virus glycoprotein D that stimulates the production of neutralizing antibody. J Virol. 1984 Jan;49(1):102–108. doi: 10.1128/jvi.49.1.102-108.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dix R. D., McKendall R. R., Baringer J. R. Comparative neurovirulence of herpes simplex virus type 1 strains after peripheral or intracerebral inoculation of BALB/c mice. Infect Immun. 1983 Apr;40(1):103–112. doi: 10.1128/iai.40.1.103-112.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dowler K. W., Veltri R. W. In vitro neutralization of HSV-2: inhibition by binding of normal IgG and purified Fc to virion Fc receptor (FcR). J Med Virol. 1984;13(3):251–259. doi: 10.1002/jmv.1890130307. [DOI] [PubMed] [Google Scholar]
  13. Ehlenberger A. G., Nussenzweig V. The role of membrane receptors for C3b and C3d in phagocytosis. J Exp Med. 1977 Feb 1;145(2):357–371. doi: 10.1084/jem.145.2.357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fearon D. T. Regulation of the amplification C3 convertase of human complement by an inhibitory protein isolated from human erythrocyte membrane. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5867–5871. doi: 10.1073/pnas.76.11.5867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Fearon D. T. The human C3b receptor. Springer Semin Immunopathol. 1983;6(2-3):159–172. doi: 10.1007/BF00205871. [DOI] [PubMed] [Google Scholar]
  16. Friedman H. M., Cohen G. H., Eisenberg R. J., Seidel C. A., Cines D. B. Glycoprotein C of herpes simplex virus 1 acts as a receptor for the C3b complement component on infected cells. Nature. 1984 Jun 14;309(5969):633–635. doi: 10.1038/309633a0. [DOI] [PubMed] [Google Scholar]
  17. Glorioso J., Kees U., Kümel G., Kirchner H., Krammer P. H. Identification of herpes simplex virus type 1 (HSV-1) glycoprotein gC as the immunodominant antigen for HSV-1-specific memory cytotoxic T lymphocytes. J Immunol. 1985 Jul;135(1):575–582. [PubMed] [Google Scholar]
  18. Heine J. W., Honess R. W., Cassai E., Roizman B. Proteins specified by herpes simplex virus. XII. The virion polypeptides of type 1 strains. J Virol. 1974 Sep;14(3):640–651. doi: 10.1128/jvi.14.3.640-651.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Holland T. C., Homa F. L., Marlin S. D., Levine M., Glorioso J. Herpes simplex virus type 1 glycoprotein C-negative mutants exhibit multiple phenotypes, including secretion of truncated glycoproteins. J Virol. 1984 Nov;52(2):566–574. doi: 10.1128/jvi.52.2.566-574.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Holland T. C., Marlin S. D., Levine M., Glorioso J. Antigenic variants of herpes simplex virus selected with glycoprotein-specific monoclonal antibodies. J Virol. 1983 Feb;45(2):672–682. doi: 10.1128/jvi.45.2.672-682.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Iida K., Nussenzweig V. Complement receptor is an inhibitor of the complement cascade. J Exp Med. 1981 May 1;153(5):1138–1150. doi: 10.1084/jem.153.5.1138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Johansson P. J., Myhre E. B., Blomberg J. Specificity of Fc receptors induced by herpes simplex virus type 1: comparison of immunoglobulin G from different animal species. J Virol. 1985 Nov;56(2):489–494. doi: 10.1128/jvi.56.2.489-494.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kikuchi G. E., Coligan J. E., Holland T. C., Levine M., Glorioso J. C., Nairn R. Biochemical characterization of peptides from herpes simplex virus glycoprotein gC: loss of CNBr fragments from the carboxy terminus of truncated, secreted gC molecules. J Virol. 1984 Dec;52(3):806–815. doi: 10.1128/jvi.52.3.806-815.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kümel G., Kaerner H. C., Levine M., Schröder C. H., Glorioso J. C. Passive immune protection by herpes simplex virus-specific monoclonal antibodies and monoclonal antibody-resistant mutants altered in pathogenicity. J Virol. 1985 Dec;56(3):930–937. doi: 10.1128/jvi.56.3.930-937.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lawman M. J., Courtney R. J., Eberle R., Schaffer P. A., O'Hara M. K., Rouse B. T. Cell-mediated immunity to herpes simplex virus: specificity of cytotoxic T cells. Infect Immun. 1980 Nov;30(2):451–461. doi: 10.1128/iai.30.2.451-461.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Little S. P., Jofre J. T., Courtney R. J., Schaffer P. A. A virion-associated glycoprotein essential for infectivity of herpes simplex virus type 1. Virology. 1981 Nov;115(1):149–160. doi: 10.1016/0042-6822(81)90097-0. [DOI] [PubMed] [Google Scholar]
  27. Manservigi R., Spear P. G., Buchan A. Cell fusion induced by herpes simplex virus is promoted and suppressed by different viral glycoproteins. Proc Natl Acad Sci U S A. 1977 Sep;74(9):3913–3917. doi: 10.1073/pnas.74.9.3913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Marlin S. D., Holland T. C., Levine M., Glorioso J. C. Epitopes of herpes simplex virus type 1 glycoprotein gC are clustered in two distinct antigenic sites. J Virol. 1985 Jan;53(1):128–136. doi: 10.1128/jvi.53.1.128-136.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Noble A. G., Lee G. T., Sprague R., Parish M. L., Spear P. G. Anti-gD monoclonal antibodies inhibit cell fusion induced by herpes simplex virus type 1. Virology. 1983 Aug;129(1):218–224. doi: 10.1016/0042-6822(83)90409-9. [DOI] [PubMed] [Google Scholar]
  30. Para M. F., Baucke R. B., Spear P. G. Glycoprotein gE of herpes simplex virus type 1: effects of anti-gE on virion infectivity and on virus-induced fc-binding receptors. J Virol. 1982 Jan;41(1):129–136. doi: 10.1128/jvi.41.1.129-136.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Para M. F., Goldstein L., Spear P. G. Similarities and differences in the Fc-binding glycoprotein (gE) of herpes simplex virus types 1 and 2 and tentative mapping of the viral gene for this glycoprotein. J Virol. 1982 Jan;41(1):137–144. doi: 10.1128/jvi.41.1.137-144.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Pereira L., Dondero D. V., Gallo D., Devlin V., Woodie J. D. Serological analysis of herpes simplex virus types 1 and 2 with monoclonal antibodies. Infect Immun. 1982 Jan;35(1):363–367. doi: 10.1128/iai.35.1.363-367.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Richman D. D., Buckmaster A., Bell S., Hodgman C., Minson A. C. Identification of a new glycoprotein of herpes simplex virus type 1 and genetic mapping of the gene that codes for it. J Virol. 1986 Feb;57(2):647–655. doi: 10.1128/jvi.57.2.647-655.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ross C., Glorioso J., Sacks S., Lavery C., Rawls W. E. Competitive inhibition by human sera of mouse monoclonal antibody binding to glycoproteins C and D of herpes simplex virus types 1 and 2. J Virol. 1985 Jun;54(3):851–855. doi: 10.1128/jvi.54.3.851-855.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Sarmiento M., Haffey M., Spear P. G. Membrane proteins specified by herpes simplex viruses. III. Role of glycoprotein VP7(B2) in virion infectivity. J Virol. 1979 Mar;29(3):1149–1158. doi: 10.1128/jvi.29.3.1149-1158.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Smiley M. L., Friedman H. M. Binding of complement component C3b to glycoprotein C is modulated by sialic acid on herpes simplex virus type 1-infected cells. J Virol. 1985 Sep;55(3):857–861. doi: 10.1128/jvi.55.3.857-861.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Smiley M. L., Hoxie J. A., Friedman H. M. Herpes simplex virus type 1 infection of endothelial, epithelial, and fibroblast cells induces a receptor for C3b. J Immunol. 1985 Apr;134(4):2673–2678. [PubMed] [Google Scholar]
  38. Spear P. G. Membrane proteins specified by herpes simplex viruses. I. Identification of four glycoprotein precursors and their products in type 1-infected cells. J Virol. 1976 Mar;17(3):991–1008. doi: 10.1128/jvi.17.3.991-1008.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES