1887

Abstract

Summary

Four monoclonal antibodies to glycoprotein D (gD) of herpes simplex virus (HSV) types 1 and 2 neutralized virus in the presence of complement but exhibited diverse activities in its absence. Amino acid substitutions that conferred resistance to neutralization by each antibody were identified by deriving the nucleotide sequence of the gD gene from resistant mutants. Each antibody selected a substitution from different parts of the molecule and mutants resistant to a single antibody always arose from the same mutation. One of the antibodies reacted with a synthetic oligopeptide corresponding to the region of the molecule in which amino acid substitution conferred resistance, but the remaining three antibodies failed to react with predicted oligopeptide targets. These antibodies may therefore react with ‘discontinuous’ epitopes, a view supported by the observation that two of these three antibodies competed with each other in binding assays despite the fact that substitutions conferring resistance to neutralization arose nearly 100 residues apart in the primary sequence. The four antibodies had very different biological properties. One antibody neutralized infectivity but did not inhibit cell fusion, one antibody inhibited cell fusion but did not neutralize, while a third antibody had both activities. One antibody had neither activity but enhanced the infectivity of HSV-2 in a type-specific manner. The ability of antibodies to inhibit cell fusion by syncytial virus strains correlated with an ability to prevent plaque enlargement by a non-syncytial virus strain, implying a role for gD in the intercellular spread of virus that is independent of the syncytial phenotype. We found no correlation between neutralizing activity and anti-fusion activity suggesting that, while gD is involved in cell fusion, it has at least one other function which is required for infectivity.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-67-6-1001
1986-06-01
2022-09-24
Loading full text...

Full text loading...

/deliver/fulltext/jgv/67/6/JV0670061001.html?itemId=/content/journal/jgv/10.1099/0022-1317-67-6-1001&mimeType=html&fmt=ahah

References

  1. Al-Moudallal Z., Briand J. B., Van Regenmortel M. H. V. 1982; Monoclonal antibodies as probes of the antigenic structure of tobacco mosaic virus. EMBO Journal 1:1005–1010
    [Google Scholar]
  2. Bankier A. J., Barrell B. G. 1983; Shotgun DNA sequencing. In Techniques in the Life Sciences vol B508 pp 1–34 Edited by Flavell R. A. Ireland: Elsevier;
    [Google Scholar]
  3. Bond V. C., Person S. 1984; Fine structure physical map locations of alterations that affect cell fusion in herpes simplex virus type 1. Virology 132:368–376
    [Google Scholar]
  4. Buckmaster E. A., Gompels U., Minson A. C. 1984; Characterisation and physical mapping of an HSV-1 glycoprotein of approximately 115 × 103 molecular weight. Virology 139:408–413
    [Google Scholar]
  5. Bzik D. J., Fox B. A., Deluca N. A., Person S. 1984; Nucleotide sequence of a region of the herpes simplex virus type 1 gB glycoprotein gene: mutations affecting rate of virus entry and cell fusion. Virology 137:185–190
    [Google Scholar]
  6. Chan W. 1983; Protective immunisation of mice with specific HSV-1 glycoproteins. Immunology 49:343–352
    [Google Scholar]
  7. Cohen G. H., Ponce De Leon M., Nichols C. 1972; Isolation of a herpes simplex virus-specific antigenic fraction which stimulates the production of neutralising antibody. Journal of Virology 10:1021–1030
    [Google Scholar]
  8. Cohen G. H., Katze M., Hydrean-Stern C., Eisenberg R. J. 1978; Type common CP-1 antigen of herpes simplex virus is associated with a 59, 000 molecular weight envelope glycoprotein. Journal of Virology 27:172–181
    [Google Scholar]
  9. Debroy C., Pederson N., Person S. 1985; Nucleotide sequence of a herpes simplex virus type 1 gene that causes cell fusion. Virology 145:36–48
    [Google Scholar]
  10. Deininger P. L. 1983; Random subcloning of sonicated DNA: application to shotgun DNA sequence analysis. Analytical Biochemistry 129:216–223
    [Google Scholar]
  11. Diamond D. C., Jameson B. A., Bonin J., Kohara M., Abe H., Itoh S., Komatsu T., Arita M., Kuge S., Nomoto A., Osterhaus A.D. M. E., Crainic R., Wimmer E. 1985; Antigenic variation and resistance to neutralisation in poliovirus type 1. Science 229:1090–1093
    [Google Scholar]
  12. Dietzschold B., Eisenberg R. J., Ponce De Leon M., Golub E., Hudecz F., Varrichio A., Cohen G. H. 1984; Fine structure analysis of type specific and type common antigenic sites of herpes simplex virus glycoprotein D. Journal of Virology 52:431–435
    [Google Scholar]
  13. Eisenberg R. J., Long D., Pereira L., Hampar B., Zweig M., Cohen G. H. 1982; Effect of monoclonal antibody on limited proteolysis of native glycoprotein D of herpes simplex type 1. Journal of Virology 41:478–488
    [Google Scholar]
  14. Eisenberg R. J., Long D., Hogue-Angeletti R., Cohen G. 1984; Amino terminal sequence of glycoprotein D of herpes simplex virus types 1 and 2. Journal of Virology 49:265–268
    [Google Scholar]
  15. Eisenberg R. J., Long D., Ponce De Leon M., Matthews J. T., Spear P. G., Gibson M. G., Laskey L. A., Berman P., Golub E., Cohen G. H. 1985; Localisation of epitopes of herpes simplex virus type 1 glycoprotein D. Journal of Virology 53:634–644
    [Google Scholar]
  16. Fuller A. E., Spear P. G. 1985; Specificities of monoclonal and polyclonal antibodies that inhibit adsorption of herpes simplex virus to cells and lack of inhibition by potent neutralising antibodies. Journal of Virology 55:475–482
    [Google Scholar]
  17. Garnier J., Osguthorpe D. J., Robson B. 1978; Analysis of the accuracy and implication of simple methods for predicting secondary structure of globular proteins. Journal of Molecular Biology 120:97–120
    [Google Scholar]
  18. Guesdon J., Ternynek T., Avrameas S. 1979; The use of avidin-biotin interaction in immuno-enzymatic techniques. Journal of Histochemistry and Cytochemistry 27:1137–1139
    [Google Scholar]
  19. Honess R. W., Watson D. H. 1974; Herpes simplex virus-specific polypeptides studied by polyacrylamide gel electrophoresis of immune precipitates. Journal of General Virology 22:171–185
    [Google Scholar]
  20. Honess R. W., Buchan A., Halliburton I. W., Watson D. H. 1980; Recombination and linkage between structural and regulatory genes of herpes simplex virus type 1: study of the functional organisation of the genome. Journal of Virology 34:716–742
    [Google Scholar]
  21. Hopp T., Woods K. 1981; Prediction of protein antigenic determinants from amino acid sequence. Proceedings of the National Academy of Sciences, U.S.A 78:3824–3828
    [Google Scholar]
  22. Knossow M., Daniels R. S., Douglas A. R., Skehel J. J., Wiley D. C. 1984; Three dimensional structure of an antigenic mutant of the influenza virus haemagglutinin. Nature, London 311:678–680
    [Google Scholar]
  23. Lasky L. A., Dowbenko C. C., Simonsen C. C., Berman P. W. 1984; Protection of mice from lethal herpes simplex virus infection by vaccination with a secreted form of cloned glycoprotein D. Biotechnology 2:527–532
    [Google Scholar]
  24. Long D., Madara T. J., Ponce De Leon M., Cohen G. H., Montgomery P. C., Eisenberg R. J. 1984; Glycoprotein D protects mice from lethal challenge with herpes simplex virus types 1 and 2. Infection and Immunity 37:761–764
    [Google Scholar]
  25. 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]
  26. Mcknight S. 1980; The nucleotide sequence and transcript map of the herpes simplex virus thymidine kinase gene. Nucleic Acids Research 8:5949–5964
    [Google Scholar]
  27. Mclean C., Buckmaster A., Hancock D., Buchan A., Fuller A., Minson A. 1982; Monoclonal antibodies to three non-glycosylated antigens of herpes simplex virus type 2. Journal of General Virology 63:297–305
    [Google Scholar]
  28. Manservigi R., Spear P. G., Buchan A. 1977; Cell fusion induced by herpes simplex virus is prompted and suppressed by different viral glycoproteins. Proceedings of the National Academy of Sciences, U.S.A 74:3913–3917
    [Google Scholar]
  29. Messing J., Vieira J. 1982; A new pair of M13 vectors for selecting either strand of double-digest restriction fragments. Gene 19:269–276
    [Google Scholar]
  30. Noble A. G., Lee G. T. Y., Sprague R., Parish M. L., Spear P. G. 1983; Anti-gD monoclonal antibodies inhibit cell fusion induced by herpes simplex virus type 1. Virology 129:218–224
    [Google Scholar]
  31. Para M., Parish M., Noble A. G., Spear P. G. 1985; Potent neutralising activity associated with anti glycoprotein D specificity among monoclonal antibodies selected for binding to herpes simplex virions. Journal of Virology 55:483–488
    [Google Scholar]
  32. Peiris J. S. M., Porterfield J. S. 1979; Antibody mediated enhancement of flavivirus replication in macrophage-like cell lines. Nature, London 382:509–511
    [Google Scholar]
  33. Rawls W. E., Balachandran N., Sisson G., Watson R. J. 1984; Localisation of a type specific antigenic site on herpes simplex virus type 2 glycoprotein D. Journal of Virology 51:263–265
    [Google Scholar]
  34. Richman D. D., Cleveland P. H., Oxman M. N. 1982; A rapid enzyme immunofiltration technique using monoclonal antibodies to serotype herpes simplex virus. Journal of Medical Virology 9:299–309
    [Google Scholar]
  35. Robson B., Suzuki E. 1976; Conformational properties of amino acid residues in globular proteins. Journal of Molecular Biology 107:327–356
    [Google Scholar]
  36. 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]
  37. Sanger F., Coulson A. R., Barrell B. G., Smith A. J. H., Roe B. 1980; Cloning in a single stranded bacteriophage as an aid to rapid DNA sequencing. Journal of Molecular Biology 143:161–178
    [Google Scholar]
  38. Sim C., Watson D. H. 1973; The role of type specific and cross reacting structural antigens in the neutralization of herpes simplex virus types 1 and 2. Journal of General Virology 19:217–233
    [Google Scholar]
  39. Simmons A., Nash A. 1985; Role of antibody in primary and recurrent herpes simplex virus infection. Journal of Virology 53:944–948
    [Google Scholar]
  40. Wagner M. J., Sharp J. A., Summers W. C. 1981; Nucleotide sequence of the thymidine kinase gene of herpes simplex type 1. Proceedings of the National Academy of Sciences, U.S.A. 78:1441–1445
    [Google Scholar]
  41. Watson R. J. 1983; DNA sequence of the herpes simplex virus type 2 glycoprotein D gene. Gene 26:307–312
    [Google Scholar]
  42. Watson R. J., Weis J. H., Salstrom J. S., Enquist L. W. 1982; Herpes simplex virus type 1 glycoprotein D gene. Nucleotide sequence and expression in E. coli . Science 218:381–384
    [Google Scholar]
  43. Williamson M. P., Handa B. K., Hall M. J. 1986; The secondary structure of a herpes simplex virus glycoprotein D antigen domain. International Journal of Peptide and Protein Research (in press)
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-67-6-1001
Loading
/content/journal/jgv/10.1099/0022-1317-67-6-1001
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

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